Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

Assessment, surveillance and prognosis in pre-eclampsia

Beth Payne, BSc, PIERS Research Manager a, d, *,
Laura A. Magee, MD, FRCPC, MSc, Clinical Associate Professor a, b, c,
Peter von Dadelszen, MBChB, DPhil, FRCSC, Associate Professor a, b, d
a

Department of Obstetrics and Gynaecology, University of British Columbia, 2H30-4500 Oak Street, BC V6H 3NI, Canada
School of Population and Public Health, University of British Columbia, 2H30-4500 Oak Street, BC V6H 3NI, Canada
Department of Medicine, University of British Columbia, 2H30-4500 Oak Street, BC V6H 3NI, Canada
d
The CFRI Reproduction and Healthy Pregnancy Cluster, University of British Columbia, 2H30-4500 Oak Street, BC V6H 3NI, Canada
b
c

Keywords:
prognosis
assessment
PIERS
pre-eclampsia

The hypertensive disorders of pregnancy (HDP) remain one of the

major causes of maternal mortality and morbidity worldwide. Many
international guidelines exist for the classication and assessment of
women with hypertension in pregnancy, but denitions and recommendations within these documents are variable. Many recommended investigations do not actually correlate with increased risk of
adverse outcomes, making it difcult to determine true prognosis.
Although standardised assessment and surveillance has been shown
to improve outcomes, the application of these monitoring strategies
in many areas of the world is not possible owing to the cost associated
with them. Not all of the tests recommended for surveillance of
women with pre-eclampsia are independently predictive of adverse
outcomes, and many unnecessary tests could be avoided if those tests
that are most informative where identied. The Pre-eclampsia Integrated Estimate of RiSk study has identied a group of tests that can be
used to predict risk of outcomes accurately up to 7 days after
admission to a tertiary hospital with pre-eclampsia. This model needs
to be validated in new populations and in different clinical settings
before it can be implemented into clinical practice. Until this happens,
clinicians should consider the whole clinical picture when assessing
women with pre-eclampsia and making decisions around expectant
management compared with stabilisation and delivery. Future

* 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).
1521-6934/$ see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bpobgyn.2011.02.003

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B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462

research in the area of prognosis should focus on women with variable

denitions of pre-eclampsia and the other HDP. All studies reviewed
were limited to cases of severe pre-eclampsia, and results may not be
generalisable across the spectrum of the disorder.
2011 Elsevier Ltd. All rights reserved.

Introduction
The hypertensive disorders of pregnancy (HDP), including chronic hypertension, gestational
hypertension and pre-eclampsia, are of great concern to clinicians because of the associated adverse
maternal and fetal outcomes. The HDP, specically pre-eclampsia, remain one of the top four causes of
maternal mortality and morbidity in high-, middle-, and low-income countries.14 Most deaths associated with these disorders occur in low- and middle-income countries.
In high-income countries, where maternal mortality is rare, severe morbidities resulting from HDP
are of greater concern. Adverse maternal outcomes associated with HDP are a result of excessive
inammation and endothelial damage, and include eclampsia, stroke, retinal detatchment, acute renal
failure, placental abruption, pulmonary oedema, liver haematoma, disseminated intravascular coagulation and cerebrovascular bleeding.5,6 Fetal complicationss include stillbirth, intracranial haemorrhage, oligohydramnios and fetal growth restriction.5 Both maternal and fetal outcomes tend to cluster
around the diagnosis of pre-eclampsia (gestational hypertension and proteinuria), but gestational
hypertension alone and other atypical forms of the disorder are not benign.710 Studies have found that
1556% of women who initially present with gestational hypertension will progress to a diagnosis of
pre-eclampsia.7,9,11 It is estimated that 15% of cases of severe pre-eclampsia, however dened, will
result in signicant maternal morbidity.12 This variability in presentation and progression presents
a signicant challenge for effective management of the HDP.
Despite recent advances in our understanding of the pathophysiology of pre-eclampsia5,13 delivery
of the placenta remains the only cure. When presenting early in gestation, delivery is not always the
best option for the fetus. Iatrogenic preterm delivery is associated with increased risks, whether it
occurs in the early or late preterm period.14 Evidence from cohort studies and randomised-controlled
trials show that, remote from term, prolongation of pregnancy by expectant management decreases
serious perinatal morbidity without signicant increases in maternal risk.1518 Uncertainty, however,
remains around the magnitude of maternal risk associated with expectant management, as randomised-controlled trials were limited to women with severe pre-eclampsia and underpowered to detect
a 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 and
avoiding associated adverse maternal and fetal outcomes. Several international guidelines for the
management of women with hypertension in pregnancy exist. In this chapter we will review the
classication systems provided in four of the more recently published guidelines, as well as their
recommendations for assessment and surveillance.2124 The evidence to support these recommendations, based on each suggested investigations ability to predict adverse maternal outcomes, will be
reviewed, primarily focusing on the recommendations for maternal assessment. In addition, results
from studies on multivariate prognostic models for the assessment of women with pre-eclampsia will
be reviewed.
International guidelines for classifying and monitoring hypertensive disorders of pregnancy
The international guidelines reviewed here were intended to provide useful criteria for diagnosis
and risk stratication, and effective management strategies in order to guide care and ultimately
reduce adverse outcomes. Unfortunately, consensus amongst these documents relating to denitions
and management strategies is lacking, and is confusing for clinicians.25 In addition, many of the criteria
for severity stipulated in these guidelines have not been properly evaluated on the basis of their
prognostic value. An overview of the classication systems is presented in Table 1. Severity criteria and
denitions for HDP are presented from the UKs National Institute for Health and Clinical Excellence

Table 1
Denitions: an international comparison between recent classication systems.
SOGC (2008)

ASH (2008)

Chronic hypertension:
essential
secondary
white coat
with or without
superimposed pre-eclampsia

Pre-existing hypertension:
with or without
co-morbid conditions
with or without
superimposed pre-eclampsia

Chronic hypertension:
with or without
superimposed
preeclampsia

Gestational
hypertension (blood
pressure 140/90
after 196 weeks
gestation)

Gestational hypertension:
without signicant
proteinuria

Gestational hypertension:
without signicant proteinuria
returning to normal within
12 weeks postpartum

Gestational hypertension:
with or without
co-morbid conditions
with or without
superimposed pre-eclampsia

Gestational hypertension
or transient hypertension:
blood pressure returning to
normal within 6 weeks
postpartum; Late postpartum
hypertension: blood pressure
rise developing up to 6 months
postpartum and normalised
by 1 year postpartum.

Pre-eclampsia
(clinical denition)

New hypertension (blood

pressure 140/90) presenting
after 20 weeks gestation with
clinically relevant proteinuria
(see signicant
proteinuria, below)

Gestational hypertension plus

one or more of the following:
dipstick proteinuria conrmed
by either random
proteincreatinine ratio
>30 mg/mmol or 0.3 g every 24 h
serum or plasma
creatinine >90 mM
oliguria
thrombocytopoaenia
haemolysis
disseminated
intravascular coagulation
raised serum transaminases
severe epigastric or right upper
quadrant pain
eclampsia
Hypereexia with sustained clonus
severe headache
persistent visual disturbances
stroke
pulmonary oedema
fetal growth restriction
placental abruption

Pre-existing hypertension and

resistant hypertension, new
proteinuria, or adverse condition
(see severity criteria, below)
Gestational hypertension plus
proteinuria (spot proteincreatinine
ratio >30 mg/mmol or 0.3 g
every 24 h), or adverse condition

Gestational hypertension or
Chronic hypertension
with proteinuria
(dipstick  1, spot
proteincreatinine
ratio 30 mg/mmol
or 0.3 g every 24 h).

(continued on next page)

451

SOMANZ (2008)

Chronic hypertension:
before 20 weeks
gestation or being treated
at time of referral
primary or secondary
aetiology

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462

NICE (2010)
Pre-existing or chronic
hypertension (blood
pressure 140/90
before 200 weeks
gestation)

452

Table 1 (continued )
SOMANZ (2008)

SOGC (2008)

ASH (2008)

Not dened

Denovo hypertension >200 weeks,

returning to normal postpartum with
properly documented proteinuria

Not dened

Not dened

Severe hypertension

160/110 mmHg

170/110 mmHg

160/110 mmHg

160/110 mmHg

Signicant proteinuria

>300 mg/d
or >30 mg/mmol
on spot
proteincreatinine ratio

Not dened

>300 mg/d or >30 mg/mmol on

spot proteincreatinine ratio

>300 mg/d
or >30 mg/mmol on
spot proteincreatinine

Severity criteria

Severe hypertension
Maternal symptoms (vision
problems, severe headache,
epigastric pain, vomiting,
papiloedema)
Biochemical abnormalities or
haematological impairment
(platelet count <100 x 109/l or
AST/ALT >70 U/L, elevated
serum creatinine)

Not dened

Gestational age at onset <340 weeks

heavy proteinuria
Maternal symptoms (persistent, new
or unusual headache, visual
disturbances, persistent abdominal
or right upper quadrant pain, severe
nausea or vomiting, chest pain
or dyspnoea)
Maternal signs of end-organ
dysfunction (eclampsia, severe
hypertension, pulmonary oedema,
or suspected placental abruption)
Abnormal maternal laboratory
testing (elevated serum creatinine;
elevated AST, ALT or LDH with
symptoms; platelet
count <100  109/L; or
serum albumin <20 g/L)
Fetal morbidity (oligohydramnios,
intrauterine growth restriction,
absent or reversed end-diastolic
ow in the umbilical artery by
Doppler velocimetry).
Intrauterine fetal death

<35 weeks gestation

Maternal symptoms
(headache, visual
disturbances,
abdominal pain)
Severe diastolic
hypertension
(>110 mmHg)
Signicant proteinuria
or oliguria
Increased serum creatinine
Decreased glomerular
ltration rate
Increased AST or LDH
Fetal morbidity
(non-reassuring
cardiotogograph)

ALT, alanine transaminase; AST, aspartate transaminase; LDH, lactate dehydrogenase; PIH, pregnancy-induced hypertension; NICE, National Institute for health and Clinical Excellence;
SOMANZ, Society of Obstetric Medicine of Australia and New Zealand; SOGC, Society of Obstericians and Gynaecologists of Canada.

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462

NICE (2010)
Pre-eclampsia
(research denition)

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453

(NICE),24 the Society of Obstetricians and Gynaecologists of Canada (SOGC),21 the American Society of
Hypertension (ASH)23 and the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ).22
Denitions of HDP are subdivided into chronic hypertension, gestational hypertension, and preeclampsia. Pre-eclampsia is then further dened as severe or non-severe, based on the presence or
absence of a variety of additional signs, symptoms and laboratory ndings. For all classication
systems, hypertension is dened as systolic blood pressure greater than or equal to 140 mmHg, diastolic 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 several
weeks postpartum, making decisions around care based on that diagnosis difcult.
For both the NICE24 and SOMANZ22 guidelines, recommendations for maternal assessment and
surveillance differ on the basis of the diagnosis, as outlined in Table 2. In the NICE24 guidelines, these
monitoring strategies also depend on severity of hypertension, where more intense and regular
surveillance is recommended for women with severe hypertension greater than 160/110 mmHg. In
contrast, the SOGC21 recommends that the same monitoring strategy is used for all cases, regardless of
diagnosis. Increased monitoring for women with severe pre-eclampsia, and consequently less monitoring for with what is felt to be milder disorder, reects an attempt to reduce unnecessary interventions and testing in women felt to have less severe disease (better prognosis), therefore reducing
costs. 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 an
adverse health outcome during the course of that persons care. Having the ability to predict the
likelihood of an individual developing a poor outcome based on that individuals clinical picture is
critical for decision making by both the healthcare provider and patient.27 Any classication system
and 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 laboratory investigations in women with pre-eclampsia are reviewed. Guidelines used for reviewing
prognostic studies are presented in Table 3.2830 Studies were included if they reported on the associated risk, or prognostic value of the predictor, with adverse maternal, fetal outcomes, or both. It is
important to distinguish the identication of a risk factor and a prognostic factor. These concepts are
often used interchangeably in the published studies, but are actually very different. Risk factors have
a causal association with the adverse outcome, with the strength of this association generally
expressed as an odds ratio or relative risk. Prognostic factors, on the other hand, give information on
the absolute probability of an outcome, independent of causation.27,31,32 Prognostic value is generally
expressed in terms of likelihood ratios, sensitivity, specicity, positive predictive value or negative
predictive 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 as
a severity criterion for pre-eclampsia. Most of the studies found reported only the association between
high blood pressure and adverse outcomes, not its prognostic value. In one case study, which included
28 women diagnosed with pre-eclampsia, systolic blood pressure greater than160 mmHg was shown
to be an independent risk factor for stroke.33 In another study, which included 216 women diagnosed
with HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome or severe pre-eclampsia
using the ASH criteria,23 diastolic blood pressure at inclusion greater than 105 mmHg was shown to be
associated with a reduced risk of adverse maternal outcomes (OR 0.66; 95% CI 0.45 to 0.96).18 In other
studies, 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 study
included 1259 women diagnosed with pre-eclampsia, as dened by the SOGC,21 and found that neither
diastolic blood pressure nor systolic blood pressure adequately predicted a combined adverse maternal
outcome alone (AUC ROC diastolic blood pressure: 0.664; 95% CI 0.579 to 0.748; systolic blood

454

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

Investigations for
ongoing monitoring

Timing of investigations

NICE (2010)

SOMANZ (2008)

SOGC (2008)

For gestational hypertension

and mild hypertension:
routine antenatal surveillance
For gestational hypertension and
moderate or severe hypertension
or pre-eclampsia:
blood pressure, kidney function,
electrolytes, full blood count,
transaminases, and bilirubin
For gestational hypertension
and mild hypertension:
routine antenatal surveillance
For gestational hypertension and
moderate or severe hypertension
or pre-eclampsia:
blood pressure, kidney function,
electrolytes, full blood count,
transaminases, and bilirubin
Blood pressure four times a day
unless 160/110 mmHg then blood
pressure more than four times per
day depending on clinical circumstances

Assessment of symptoms, blood

pressure, urine dipstick and
proteinuria by spot or 24 h if
dipstick  1, full blood count,
urea, creatinine, electrolytes
and liver function

Blood pressure, haemoglobin, WBC and

differential, platelet count, blood lm, INR
and aPTT, brinogen, serum creatinine,
serum uric acid, glucose, AST, ALT, LDH,
albumin, billirubin, urinalysis (routine and
microscopy), proteinuria (assessed by
urinary protein dipstick, spot
proteincreatinine ratio, or 24 h urinalysis)

Assessment of symptoms, blood

pressure, urine dipstick and
proteinuria by spot or 24 h if
dipstick  1, full blood count,
urea, creatinine, electrolytes
and liver function

Blood pressure, haemoglobin, WBC and

differential, platelet count, INR and aPTT,a
brinogen,a serum creatinine, serum uric
acid, AST, ALT, LDH, albumin, billirubin,
proteinuria (assessed by urinary protein
dipstick, spot proteincreatinine ratio,
or 24 h urinalysis)

Urinalysis assessed at each visit until

diagnosis of pre-eclampsia made, then daily
Laboratory blood investigations
twice weekly or more if unstable

Serial surveillance of blood

pressure and proteinuria:
laboratory investigations
carried out at least once per
week antenatally and at least
once in the rst 3 days postpartum

Proteinuria at each visit until

pre-eclampsia diagnosis made
then repeat measurement
not recommended.
Blood tests two to three times a
week depending on severity of
hypertension and presence of
proteinuria
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 and
Gynaecologists of Canada; SOMANZ, Society of Obstetric Medicine of Australia and New Zealand; WBC, white blood cells.

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462

Investigations at initial
presentation

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455

Table 3
Guidelines 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 effect

of a positive test (LR) or negative test (LR)
on the post-test probability of outcome. The
further from 1, in both cases, the greater
the effect of the test.30
The receiver operating curve is a plot of sensitivity
versus 1-specicity for a test. The AUC ROC is a
measure of a tests ability to discriminate between
those patients with or without an outcome. An AUC
ROC of 1.0 gives perfect discrimination and 0.5 would
be similar to random chance29

LR >5.0 and LR <0.2

Area under the curve of

the receiver operating
characteristic (AUC ROC)

0.70

pressure: 0.690; 95% CI 0.606 to 0.775).36 No blood pressure cut-off that denes risk can be identied
on the basis of these results. The poor prognostic value of blood pressure is probably due to a highly
modiable variable within this population.
No evidence exists on the optimal timing of blood pressure monitoring, and the optimal level of
blood pressure in women with HDP remains controversial. Some evidence exists that there may be
adverse fetal growth effects owing to the drop in mean arterial pressure associated with control
of hypertension in pregnancies complicated by any form of hypertension in pregnancy.11,37,38 The goal
of monitoring blood pressure should be to balance blood pressure control for the avoidance of maternal
cerebrovascular morbidities and optimisation of fetal growth. Repeat and regular blood pressure
monitoring is recommended but no blood pressure cut-off has been identied that can be used to
dene risk.
Proteinuria
New onset of proteinuria in pregnancies complicated by hypertension has formed the basis of the
clinical 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 the
SOGC21and ASH23 guidelines. More recently, the role of proteinuria measurement in the classication
of pre-eclampsia has been called into question.39 Inaccuracies have been identied with the goldstandard 24-h urine collection method,40 prompting investigation into the utility of other methods of
measuring proteinuria in hypertensive pregnancies. The spot proteincreatinine ratio test has been
recommended by both NICE24 and SOMANZ22 as an acceptable method of testing proteinuria in this
population. Results from a systematic review have suggested that using 30 mg/mmol as a threshold for
the spot proteincreatinine ratio is a reasonable alternative to 0.3 g/day to rule-out proteinuria in
hypertensive pregnancies (sensitivity 83.6%; 95% CI 77.5 to 89.7% and specicity 77.5%; 95% CI 72.6 to
80.0%).41 These thresholds, however, were chosen somewhat arbitrarily and require further validation.
The occurrence of proteinuria in women with pre-eclampsia has been shown to be associated with
some increased perinatal risks but not necessarily maternal risks. In one study, which included 1348
women diagnosed with pre-eclampsia using the International Society for the Study of Hypertension in
Pregnancy classication system,25 the occurrence of proteinuric pre-eclampsia was associated with
signicantly increased odds of preterm birth (OR 1.46; 95% CI 1.11 to 1.92) and perinatal mortality (OR
4.28; 95% CI 1.01 to 18.16), and showed a trend towards more severe hypertension (OR 1.28; 95% CI 0.98
to 1.68) compared with women with non-proteinuric pre-eclampsia.8 A subset of 321 women was
included in this study, and the prognostic value of proteinuria measured by spot proteincreatinine
ratio was investigated. The nal model developed in this study included both spot proteincreatinine
ratio and maternal age with an AUC ROC of 0.67 for prediction of maternal adverse outcomes. Maternal
age was included because investigators found that increased maternal age reduced the level of
proteinuria required to be predictive of adverse outcomes. This same study found that no level
of proteinuria could be dened to predict outcomes accurately, leading to the conclusion that presence
of proteinuria rather than magnitude is more reective of risk.42

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A systematic review of proteinuria measured by 24-h urinalysis as a predictor of complications in

women with severe pre-eclampsia, variably dened, found that proteinuria is a poor predictor of either
maternal or fetal complications. Because of the heterogeneity of cut-off values used to dene
proteinuria, pooling of data was not possible. The adverse maternal outcomes investigated were
eclampsia and placental abruption and resulted in likelihood ratios for a positive and negative test that
were 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 prediction
of eclampsia. For the prediction of placental abruption, pooled LR was 0.88 (95% CI 0.42 to 1.86) and
LR was 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-eclampsia
Integrated Estimate of RiSk (PIERS) study, a prospective study of 2023 women with pre-eclampsia, in
which none of dipstick, spot proteincreatinine ratio, or the 24-h urine test predicted maternal or fetal
outcomes accurately (AUC ROC <0.7 in all cases).44 These results support the recommendation in the
NICE guideline that once proteinuria has been found, repeat measurements are not required and
should not be used to guide decisions around delivery of the fetus.24
Laboratory testing
Several laboratory tests are recommended for surveillance of women with hypertension in pregnancy. Of these tests, platelet count less than 100  109/L; elevated creatinine; elevated aspartate
transaminase (AST) or lactate dehydrogenase (LDH); and serum albumin less than 20 g/L have been
used to dene severity (Table 2), and are explicitly recommended as indications for delivery by the
SOMANZ.22 This is based on increased incidence of maternal adverse outcomes shown to occur in
women with these various criteria, but few studies have addressed whether these tests can be used to
predict the probability of adverse maternal or fetal outcomes. Indeed, in several studies that have
included women diagnosed with pre-eclampsia, platelet count less than 100  109/L was found to be
associated with increased incidence of adverse maternal and perinatal outcomes (P < 0.05 in all
cases).34,45,46 In one study, which included 1387 women in the PIERS database diagnosed with preeclampsia using the SOGC guidelines, platelet count less than 100  109/L was shown to have
borderline utility in predicting risk of adverse maternal outcomes (LR 4.05; 95% CI 2.60 to 6.31; LR
0.78; 95% CI 0.67 to 0.90).47 No studies have evaluated the prediction of adverse fetal outcomes using
platelet count.
Similarly, creatinine greater than 110 mM was shown to be associated with increased incidence of
adverse maternal outcomes (P < 0.001).34 Data from the PIERS study, including 1259 women with preeclampsia, showed that creatinine was associated with increased risk of adverse maternal outcomes in
univariate logistic regression analysis using mM as the unit of analysis (OR 1.02; 95% CI 1.02 to 1.03);
however, based on the reported AUC ROC (0.67; 95% CI 0.57 to 0.76) the test did not perform adequately
to be used alone to predict risk.36
Elevated liver enzymes have been found to be independent risk factors for adverse maternal
outcomes (P < 0.001) in women with pre-eclampsia,34,48 but not in women with HELLP syndrome.49,50
The prognostic value of liver enzymes: AST; alanine aminotransferase (ALT); and LDH, was investigated
in one study using data from 1938 women in the PIERS database. The AUC ROC for AST, ALT and LDH
were all below 0.7, and no threshold value that predicts risk could be identied. In this study, serum
albumin levels were also investigated and shown to be associated with increased risk of adverse
maternal outcomes (OR 2.5; 95% CI 1.4 to 4.6) when comparing the women in the lowest quartile
(albumin <21 g/L) to those in the highest (albumin >41 g/L), but this did not result in an adequately
discriminative test (AUC ROC 0.63; 95% CI 0.57 to 0.69).51
In addition, uric acid has been suggested to have clinical utility as a prognostic indicator of maternal
health in pre-eclampsia owing to its action on the endothelium.52 Serum uric acid levels are known to
be elevated in women with pre-eclampsia and gestational hypertension compared with normotensive
pregnant women.53 One meta-analysis has addressed the accuracy of serum uric acid as a predictor or
maternal and fetal complication in women with severe pre-eclampsia, variably dened. In a combined
cohort of 634 women, using a threshold level of 350 umol/L, serum uric acid was a poor predictor of

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457

eclampsia (pooled LR 2.1; 95% CI 1.4 to 3.5; LR0.38; 95% CI 0.18 to 0.81). No other adverse maternal
outcomes were investigated.54 In another study, which included 258 women diagnosed with severe
pre-eclampsia using criteria similar to those endorsed by the ASH,23 investigators found a moderately
increased likelihood of a combined adverse maternal outcome with a positive test using a threshold
value 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 the
heterogeneity of denitions and thresholds used in studies, the clinical utility of uric acid measurement
remains unclear.
Despite being risk factors for adverse outcomes, none of the laboratory parameters discussed can
be used to predict adverse maternal outcomes accurately. Routine surveillance of these variables
seems appropriate but more studies are required to identify proper thresholds for severity that
would be clinically informative based on their ability to predict adverse maternal outcomes. Clinicians should recognise the poor prognostic value of these parameters and use caution when making
decisions around care of women with pre-eclampsia based solely on the presence of these risk
factors.
Oxygen saturation
No recommendations for the use of pulse oximetry in the assessment and surveillance of women
with pre-eclampsia exist. Oxygen saturation measured by pulse oximetry (SpO2) is widely used in
pediatric and adult populations to predict risk of respiratory complications and for perioperative
monitoring56,57 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 normal
oxygen saturation value during pregnancy.58
The predictive value of SpO2 in pregnancies complicated by pre-eclampsia was investigated in one
study. In this study, using a prospective cohort of 1534 women in the PIERS database, oxygen saturation
was found to be a reasonable predictor of a combined adverse maternal outcome within 48 h of
admission 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 studies
are 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 HDP
and are used to dene severity of disease by all international guidelines reviewed. The use of clinical
symptoms in pre-eclampsia is controversial, as many of these symptoms are non-specic and
common to normal pregnancy. In a small cohort of 61 women diagnosed with HELLP syndrome, the
presence of headache (OR 3.6; 95% CI 1.2 to 10.4), visual disturbances (OR 5.2; 95% CI 1.7to 15.9), and
epigastric pain (OR 3.75; 95% CI 1.04 to 13.4) were all shown to be associated with increased incidence of maternal adverse outcomes.50 In a retrospective cohort of 970 women with severe preeclampsia, with or without HELLP syndrome, one study found that nausea and vomiting and
epigastric 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 database
showed that only the symptom complex chest pain and dyspnoea was predictive of adverse maternal
outcomes, although poorly (AUC ROC 0.64; 95% CI 0.54 to to 0.74).36 These data suggest that
symptoms are of limited utility for determining risk and should not be used alone to guide clinical
decisions.
Multivariate prognostic models
Given the multi-system nature of pre-eclampsia, and the variability in presentation, it is not
surprising that no individual variable can be identied to predict adverse outcomes alone. Multivariate
prognostic models have been developed and successfully implemented in several other areas of

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medicine.6062 These models, when properly developed and validated, can be used to identify those
patients for whom intervention would be most benecial and can aid in decision making for both the
patient and healthcare provider.31 Two studies were identied that attempted to develop multivariate
prognostic models in women with pre-eclampsia.
In one study, using a prospective cohort of 216 women admitted as part of the Pre-Eclampsia Trial
Amsterdam (PETRA) study with HELLP, severe pre-eclampsia (dened by the International Society for
the Study of Hypertension in Pregnancy24), eclampsia or fetal growth restriction with gestational
hypertension, variables were evaluated on the basis of their ability to predict adverse maternal
outcomes at any time after eligibility. Variables found to be associated with the adverse outcome were
as follows: estimated fetal weight below 1100 g (RR 1.49; 95% CI 1.02 to 2.18); diastolic blood pressure
greater than 105 mmHg (RR 0.66; 95% CI 0.45 to 0.96); thrombophillic disorders (RR 1.51 95% CI 1.05 to
2.18); maternal age above 30 years (RR 0.62; 95% CI 0.42 to 0.92), and; nulliparity (RR 2.19; 95% CI 1.27
to 3.78). When these variables were included in a multivariate logistic regression analysis, the resultant
prediction model included only estimated fetal weight and nulliparity, and had poor discriminative
power (AUC ROC 0.65; no condence interval reported).18 No further analysis on the application of this
model in clinical care was justied.
The PIERS study, a prospective, multicentre observational study, was designed specically to
develop and validate a maternal outcome prediction model for women admitted to hospital with preeclampsia.63 Unlike previous studies, inclusion criteria were not limited to women with HELLP or
severe 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 Zealand
and Australia, variables including demographics, symptoms, signs and laboratory ndings were evaluated on the basis of their ability to predict adverse maternal outcomes within 48 h of eligibility or up
to 7 days after eligibility.64 This time point for outcome prediction differs from that used in the PETRA
study,18 and was chosen because it is the time frame around which decisions on corticosteroid
administration and maternal transport are made. The PIERS combined adverse maternal outcome is
given 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 was
postpartum) (OR 0.91; 95% CI 0.88 to 0.95); creatinine (OR 1.02; 95% CI 1.02 to 1.02); platelet count (OR
0.99; 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 maternal
outcomes 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, is
being developed for use in low- and middle-income country settings. Results of this study have not
been 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 to
change monitoring strategies can be made on the basis of these results. If validated, application of the
PIERS model 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 to
validate externally, and then implement, the fullPIERS model into care in new populations and clinical
settings.
Table 4
The The Pre-eclampsia Integrated Estimate of RiSk combined adverse maternal outcome.
Organ System

Outcome

Hepatic
Central nervous system

Dysfunction, failure, haematoma or rupture

Eclampsia, Glasgow Coma Score <13, stroke, reversible ischaemic neurologic decit,
cortical blindness, retinal detachment, posterior reversible encephalopathy, Bells palsy
Positive inotropic support, infusion of 3rd parenteral antihypertensive, myocardial infarction,
pulmonary oedema, >50% Fi02 for >1 h, intubation (not for caesarean)
Acute renal insufciency, acute renal failure (if pre-existing renal disease), dialysis
Transfusion

Cardiorespiratory
Renal
Haematological

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459

Standardisation of assessment and surveillance through clinical guidelines

Standardisation of care through the use of assessment and surveillance guidelines has been
shown to be effective for reducing adverse outcomes. Instituting surveillance guidelines at British
Columbia Womens Hospital and Health Centre for all women with any HDP was associated with
a drop in the incidence of adverse maternal outcomes (5.1% pre-intervention to 0.7% post-intervention; P < 0.001) but with no change in perinatal outcomes.68 When the same surveillance
guideline was actively introduced across the province of British Columbia, a reduction in incidence of
maternal (3.1% to 1.9%; P < 0.001) and perinatal (1.9% to 1.3%; P 0.006) outcomes was seen.69 This
reduction in maternal adverse outcomes was signicantly greater than that for non-hypertensive
pregnant women in the same time period, suggesting the guideline implementation itself is
responsible for the improvement. These guidelines formed the basis of recommendations made by
the SOGC in 2008.21 Similar results were seen when an active guideline implementation strategy was
used in Yorkshire.12

Conclusion
HDP remain one of the major causes of maternal mortality and morbidity worldwide. Many
international guidelines exist for the classication and assessment of women with hypertension in
pregnancy, but denitions and recommendations within these documents are variable. Many recommended investigations do not actually correlate with increased risk of adverse outcomes, making
it difcult to determine true prognosis. Although standardised assessment and surveillance has been
shown to improve outcomes, the application of these monitoring strategies in many areas of the
world is not possible owing to the cost associated with them. Not all of the tests recommended for
surveillance of women with pre-eclampsia are independently predictive of adverse outcomes, and
many 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 accurately
up to 7 days after admission to a tertiary hospital with pre-eclampsia. This model needs to be
validated in new populations and in different clinical settings before it can be implemented into
clinical practice.70 In the interim, clinicians should consider the whole clinical picture when
assessing women with pre-eclampsia and making decisions around expectant management
compared with aggressive intervention. Future research in the area of prognosis should focus on
women with variable denitions of pre-eclampsia and other HDP. All studies reviewed were limited
to cases of severe pre-eclampsia, and results may not be generalisable across the spectrum of the
disorder.

Conict of interest
None declared.

Practice points
 Current classication systems are limited in their ability to stratify women on the basis of risk
of adverse maternal outcomes.
 Individual clinical and laboratory variables suggested as severity criteria by international
guidelines are of limited prognostic value.
 The PIERS model is a multivariate prognostic model that correctly identies women at risk of
adverse outcome but requires further validation.
 Standardisation of assessment and surveillance for all women with a hypertensive disorder of
pregnancy has been shown to improve outcomes.

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Research agenda
 Identication of proper threshold for severity for common laboratory and clinical variables
used in the assessment and surveillance of women with the HDP based on their ability to
predict adverse outcomes.
 Validation of thresholds of proteinuria and uric acid that should be used for the diagnosis of
pre-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.

References
1. World Health Organization, UNICEF, UNFPA et al. Maternal mortality in 2005: estimates developed by WHO, UNICEF, UNFPA
and The World Bank 2007, http://www.who.int/making_pregnancy_safer/documents/9789241596213/en/index.html.
2. Hogan MC, Foreman KJ, Naghavi M et al. Maternal mortality for 181 countries, 1980-2008: a systematic analysis of
progress towards millennium development goal 5. Lancet 2010; 375: 16091623.
3. Souza JP, Cecatti JG, Faundes A et al. Maternal near miss and maternal death in the World Health Organizations 2005
global survey on maternal and perinatal health. Bull World Health Organ 2010; 88: 113119.
4. Moodley J. Maternal deaths due to hypertensive disorders in pregnancy: saving mothers report 2002 2004. Cardiovasc J
Afr 2007; 18: 358361.
*5. Steegers EA, von Dadelszen P, Duvekot JJ et al. Pre-eclampsia. Lancet 2010; 376: 631644.
6. Silasi M, Cohen B, Karumanchi SA et al. Abnormal placentation, angiogenic factors, and the pathogenesis of preeclampsia.
Obstet Gynecol Clin North Am 2010; 37: 239253.
7. Barton JR, Obrien JM, Bergauer NK et al. Mild gestational hypertension remote from term: progression and outcome. Am
J Obstet Gynecol 2001; 184: 979983.
8. Homer CS, Brown MA, Mangos G et al. Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational
hypertension. J Hypertens 2008; 26: 295302.
9. Saudan P, Brown MA, Buddle ML et al. Does gestational hypertension become pre-eclampsia? Br J Obstet Gynaecol 1998;
105: 11771184.
10. Sibai BM & Stella CL. Diagnosis and management of atypical preeclampsia-eclampsia. Am J Obstet Gynecol 2009; 200: 481.
e1481.e7.
11. Magee LA, von Dadelszen P, Chan S et al. The control of hypertension in pregnancy study pilot trial. BJOG 2007; 114: 770.
e13770.e20.
12. Tuffnell DJ, Jankowicz D, Lindow SW et al. Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003. BJOG
2005; 112: 875880.
13. Jim B, Sharma S, Kebede T et al. Hypertension in pregnancy: a comprehensive update. Cardiol Rev 2010; 18: 178189.
14. Khashu M, Narayanan M, Bhargava S et al. Perinatal outcomes associated with preterm birth at 33 to 36 weeks gestation:
a population-based cohort study. Pediatrics 2009; 123: 109113.
15. Haddad B & Sibai BM. Expectant management in pregnancies with severe pre-eclampsia. Semin Perinatol 2009; 33:
143151.
16. Ganzevoort W, Rep A, Bonsel GJ, et alPETRA investigators. Dynamics and incidence patterns of maternal complications in
early-onset hypertension of pregnancy. BJOG 2007; 114: 741750.
17. Magee LA, Yong PJ, Espinosa V et al. Expectant management of severe preeclampsia remote from term: a structured
systematic review. Hypertens Pregnancy 2009; 28: 312347.
18. Ganzevoort W, Rep A, de Vries JI, et alPETRA-investigators. Prediction of maternal complications and adverse infant
outcome at admission for temporizing management of early-onset severe hypertensive disorders of pregnancy. Am J
Obstet Gynecol 2006; 195: 495503.
19. Bombrys AE, Barton JR, Habli M et al. Expectant management of severe preeclampsia at 27(0/7) to 33(6/7) weeks
gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management. Am
J Perinatol 2009; 26: 441446.
20. Bombrys AE, Barton JR, Nowacki EA et al. Expectant management of severe preeclampsia at less than 27 weeks gestation:
maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management. Am J Obstet
Gynecol 2008; 199: 247.e1247.e6.
21. Magee LA, Helewa ME, Moutquin JM et al. SOGC guidelines; diagnosis, evaluation and management of the hypertensive
disorders of preganacy. J Obstet Gynaecol Can 2008; 30(3 suppl): 148.
22. Lowe SA, Brown MA, Dekker GA et al. Guidelines for the management of hypertensive disorders of pregnancy 2008. Aust N
Z J Obstet Gynaecol 2009; 49: 242246.
23. Lindheimer MD, Taler SJ, Cunningham FG, & American Society of Hypertension. ASH position paper: hypertension in
pregnancy. J Clin Hypertens (Greenwich) 2009; 11: 214225.
24. National Institute for Health and Clinical Excellence. Hypertension in pregnancy: the management of hypertensive disorders
during pregnancy (clinical guideline 107) August 2010, http://www.nice.org.uk/nicemedia/live/13098/50418/50418.pdf.
25. Brown MA, Lindheimer MD, de Swiet M et al. The classication and diagnosis of the hypertensive disorders of pregnancy:
statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001;
20: IXXIV.

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462

461

26. Visintin C, Mugglestone MA, Almerie MQ et al. Management of hypertensive disorders during pregnancy: summary of
NICE guidance. BMJ 2010; 341: c2207.
*27. Moons KGM, Royston P, Vergouwe Y et al. Prognosis and prognostic research: what, why, and how? BMJ 2009; 338: b375.
28. Hanley JA & McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology
1982; 143: 2936.
29. Bewick V, Cheek L & Ball J. Statistics review 14: logistic regression. Crit Care 2005; 9: 112118.
30. Jaeschke R, Guyatt GH, Sackett DL et al. Users guides to the medical literature.III. How to use an article about a diagnostic
test. B. what are the results and will they help me in caring for my patients. JAMA 1994; 271: 703707.
*31. Moons KGM, Altman DG, Vergouwe Y et al. Prognosis and prognostic research: application and impact of prognostic
models in clinical practice. BMJ 2009; 338: b606.
32. Hansebout RR, Cornacchi SD, Haines T et al. How to use an article about prognosis. Can J Surg 2009; 52: 328336.
33. Martin Jr. JN, Thigpen BD, Moore RC et al. Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on
systolic blood pressure. Obstet Gynecol 2005; 105: 246254. Feb.
*34. Menzies J, Magee LA, Macnab YC et al. Current CHS and NHBPEP criteria for severe preeclampsia do not uniformly predict
adverse maternal or perinatal outcomes. Hypertens Pregnancy 2007; 26: 447462.
35. Zhang J, Klebanoff MA & Roberts JM. Prediction of adverse outcomes by common denitions of hypertension in pregnancy.
Obstet Gynecol 2001; 97: 261267.
36. Menzies J, von Dadelszen P, & PIERS Study Grp. The PIERS (Pre-Eclampsia Integrated Estimate of Risk) models: univariable
and cluster analyses. Hypertens Pregnancy 2008; 27. 620620.
37. von Dadelszen P & Magee LA. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: an
updated metaregression analysis. J Obstet Gynaecol Can 2002; 24: 941945.
38. von Dadelszen P, Ornstein MP, Bull SB et al. Fall in mean arterial pressure and fetal growth restriction in pregnancy
hypertension: a meta-analysis. Lancet 2000; 355: 8792.
*39. Lindheimer MD & Kanter D. Interpreting abnormal proteinuria in pregnancy: the need for a more pathophysiological
approach. Obstet Gynecol 2010; 115: 365375.
*40. Cote AM, Firoz T, Mattman A et al. The 24-hour urine collection: gold standard or historical practice? Am J Obstet Gynecol
2008; 199: 625.e1625.e6.
41. Cote AM, Brown MA, Lam E et al. Diagnostic accuracy of urinary spot protein: creatinine ratio for proteinuria in hypertensive pregnant women: systematic review. BMJ 2008; 336: 10031006.
42. Chan P, Brown M, Simpson JM et al. Proteinuria in pre-eclampsia: how much matters? Bjog-an International J Obstet
Gynaecol 2005; 112: 280285.
43. Thangaratinam S, Coomarasamy A, OMahony F et al. Estimation of proteinuria as a predictor of complications of preeclampsia: a systematic review. BMC Med 2009; 7: 10.
44. Payne B, Magee LA, Ct AM et al.; for the PIERS group. PIERS proteinuria: relationship with adverse maternal and
perinatal outcome. J Obstet Gynaecol Can 2011; 33: xxxxxx (in press).
45. Romero R, Mazor M, Lockwood CJ et al. Clinical signicance, prevalence, and natural history of thrombocytopenia in
pregnancy-induced hypertension. Am J Perinatol 1989; 6: 3238.
46. Brown MA & Buddle ML. Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical
features. Med J Aust 1996; 165: 360365.
47. Laskin S, Payne B, Hutcheon J, et alPIERS Study Group. The role of platelet counts in the assessment on inpatient women
with pre-eclampsia. Pregnancy Hypertens 2010; 1: S7.
48. Martin Jr. JN, May WL, Magann EF et al. Early risk assessment of severe preeclampsia: admission battery of symptoms
and laboratory tests to predict likelihood of subsequent signicant maternal morbidity. Am J Obstet Gynecol 1999; 180:
14071414.
49. Haddad B, Barton JR, Livingston JC et al. Risk factors for adverse maternal outcomes among women with HELLP
(hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am J Obstet Gynecol 2000; 183: 444448.
50. Cavkaytar S, Ugurlu EN, Karaer A et al. Are clinical symptoms more predictive than laboratory parameters for adverse
maternal outcome in HELLP syndrome? Acta Obstet Gynecol Scand 2007; 86: 648651.
51. Benton SJ, von Dadelszen P, & PIERS (Pre-eclampsia Integrated Estimate of RiSk) Study Group. Abnormal liver tests as
predictors for adverse maternal outcomes in women with pre-eclampsia. Pregnancy Hypertens 2010; 1: P88.
*52. Martin AC & Brown MA. Could uric acid have a pathogenic role in pre-eclampsia? Nat Rev Nephrol 2010; 6: 744748.
53. Williams KP & Galerneau F. The role of serum uric acid as a prognostic indicator of the severity of maternal and fetal
complications in hypertensive pregnancies. J Obstet Gynaecol Can 2002; 24: 628632.
54. Thangaratinam S, Ismail KMK, Sharp S et al. TIPPS review group. Accuracy of serum uric acid in predicting complications of
pre-eclampsia: a systematic review. BJOG 2006; 113: 369378.
55. Parrish M, Grifn M, Morris R et al. Hyperuricemia facilitates the prediction of maternal and perinatal adverse outcome in
patients with severe/superimposed preeclampsia. J Matern Fetal Neonatal Med 2010; 23: 14511455.
56. Pedersen T, Moller AM & Hovhannisyan K. Pulse oximetry for perioperative monitoring. Cochrane Database of Syst Rev
2009 (4):CD002013.
57. De Felice C, Leoni L, Tommasini E et al. Maternal pulse oximetry perfusion index as a predictor of early adverse respiratory
neonatal outcome after elective cesarean delivery. Pediatr Crit Care Med 2008; 9: 203208.
58. VanHook JW, Harvey CJ & Anderson GD. Effect of pregnancy on maternal oxygen saturation values: u se of reectance
pulse oximetry during pregnancy. South Med J 1996; 89: 11881192.
59. Millman A, Payne B, von Dadelszen P. Oxygen saturation as a predictor of outcomes in women with pre-eclampsia. J Obstet
Gynaecol Can (in press).
60. Kannel WB, Mcgee D & Gordon T. General cardiovascular risk prole - framingham study. Am J Cardiol 1976; 38: 4651.
61. Wong DT & Knaus WA. Predicting outcome in critical care: the current status of the apache prognostic scoring system. Can
J Anaesth 1991; 38: 374383.
62. Richardosn DK, Corcoran JD, Escobar GJ et al. SNAP-II and SNAPPE-II: simplied newborn illness severity and mortality risk
scores. J Pediatr 2001; 138: 92100.

462

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462

63. von Dadelszen P, Magee LA, Devarakonda RM et al. The prediction of adverse maternal outcomes in preeclampsia. J Obstet
Gynaecol Can 2004; 26: 871879.
*64. von Dadelszen P, Payne B, li J et al. Prediction of adverse maternal outcomes in pre-eclampsia: the fullPIERS model:
development and validation. Lancet 2011; 377: 219227.
65. Brown B, Cochran SW & Helmer O. An evaluation of methodology of Delphi technique. Biometrics 1967; 23: 600.
66. Hutchinson A & Fowler P. Outcome measures for primary health care: what are the research priorities. Br J Gen Pract 1992;
42: 227231.
67. The PIERS Study Group. Pre-eclampsia Integrated Estimate of RiSk (PIERS). Child and family research institute; https://
piers.cfri.ca.
*68. Menzies J, Magee LA, Li J et al. Instituting surveillance guidelines and adverse outcomes in preeclampsia. Obstet Gynecol
2007; 110: 121127.
*69. von Dadelszen P, Sawchuck D, McMaster R et al. The active implementation of pregnancy hypertension guidelines in
British Columbia. Obstet Gynecol 2010; 116: 659666.
70. Altman DG, Vergouwe Y, Royston P et al. Prognosis and prognostic research: validating a prognostic model. BMJ 2009; 338:
b605.