BJOG 2000,107(2), pp.

196-208
How useful is uterine artery Doppler flow velocimetry in
the prediction of pre-eclampsia, intrauterine growth
retardation and perinatal death? An overview
"Patrick F. W. Chien Senior Lecturer (Obstetrics and Gynaecology), *Neil Arnott Specialist Registrar (Obstetrics
and Gynaecology), *Adam Gordon Specialist Registrar (Obstetrics and Gynaecology),
?Philip Owen Consultant (Obstetrics and Gynaecology), SKhalid S. Khan Lecturer (Obstetrics and Gynaecology)
*Department of Obstetrics and Gynaecology, Ninewells Hospital, Dundee; TDepartmnt of obstetrics and Gynaecology, Glasgow
Royal Maternity Hospital, Glasgow; $Department of Obstetrics and Gynaecology, University of Birmingham, Edgbaston
Objective To evaluate the clinical usefulness of Doppler analysis of the uterine artery velocity wave-
form in the prediction of pre-eclampsia and its associated complications of intrauterine growth retar-
dation and perinatal death.
Design Quantitative systematic review of observational diagnostic studies using online searching of the
MEDLINE database coupled with scanning of the bibliographies of primary and review articles
including known unpublished studies.
Material Twenty-seven studies involving 12,994 subjects stratified into population subgroups at low
and high risk of developing pre-eclampsia and its complications.
Outcome measures The outcome measures studied were: 1. the development of pre-eclampsia; 2.
intrauterine growth retardation; and 3. perinatal death. The main meta-analyses were the flow velocity
waveform ratio f diastolic notch derived by transabdominal Doppler ultrasound as the measurement
parameter. The analyses were conducted using likelihood ratio as a measure of diagnostic accuracy. A
likelihood ratio of 1 indicates that the test has no predictive value for the outcome. Prediction for the
outcome event is considered conclusive with likelihood ratios of >10 or <0.1 for a positive and neg-
ative test result, respectively. Moderate prediction can be achieved with likelihood ratios of 5-10 and
0-1-0-2 whereas likelihood ratios values of 1-5 and 0.2-1 would generate only minimal prediction.
In the low risk population a positive test result, predicted pre-eclampsia with a pooled likeli-
hood ratio of 6.4 (95% CI 5.7-7.1), while a negative test result had a pooled likelihood ratio of 0.7
(95% CI 0-6-0-8). For intrauterine growth retardation the pooled likelihood ratio was 3.6 (95% CI
3-24-0) for a positive test result and 0.8 (95% CI 0-8-0-9) for a negative test result. Using perinatal
death as outcome measure, the pooled likelihood ratio was 1.8 (95% CI 1.2-2-9) for a positive test
result and 0.9 (95% CI 0.8-1.1) for a negative test result. In the high risk population a positive test
result predicted pre-eclampsia with a pooled likelihood ratio of 2.8 (95% CI 2.3-3.4), while a nega-
tive test had a likelihood ratio of 0.8 (95% CI 0.749). For intrauterine growth retardation the pooled
likelihood ratio was 2.7 (95% CI 2.1-3.4) for a positive test result and 0.7 (95% CI 0.6-0.9) for a neg-
ative result. For perinatal death the pooled likelihood ratio was 4.0 (95% CI 2.4-6.6) for a positive test
result and 0.6 (95% CI 04-0.9) for a negative result.
Uterine artery Doppler flow velocity has limited diagnostic accuracy in predicting pre-
eclampsia, intrauterine growth retardation and perinatal death.
Results
Conclusion
INTRODUCTION 1991-1993 confirm that hypertensive disorders of
pregnancy is still the second-most common cause of
maternal mortality, accounting for 20/128 (15.5%)
direct deathsl. Hypertension in pregnancy is also
responsible for 8% of fetal (>19 weeks of gestation)
and infant mortality and 46% of infants born small for
Despite recent advances in antenatal care, pre-eclamp-
sia has remained a major cause of maternal and perina-
tal morbidity and mortality. Data from the Confidential
Enquiries into Maternal Deaths in the United Kingdom
196 0 RCOG 2000 BJOG
UTERI NE ARTERY DOPPLER FL OW VEL OCI METRY 197
biochemical measures have been found to have limited
accuracy as screening measures for this ~ondition.~.
Pre-eclampsia is characterised by an imbalance
between prostacycline and thromboxane production5, as
well as failure of the second wave trophoblastic invasion
of the endometrio- myometrial vasculature. The result is
abnormal uteroplacental blood flow, and this has lead to
the idea of using Doppler assessment of uterine artery
velocity waveforms as a method of screening for this
antenatal complication6. An abnormal test result is repre-
sented by either an abnormal flow velocity ratio (systolic
to diastolic velocity (S:D) ratio, diastolic to systolic
velocity ratio (D:S) or resistance index) or the presence
of an early diastolic notch. However, the wide variation
in scanning techniques, Doppler measurement parame-
ters and study protocols have resulted in conflicting
results3. To address these concerns and to overcome the
lack of precision in the individual studies, we decided to
conduct a quantitative systematic review of the currently
available literature in order to determine whether uterine
artery Doppler ultrasound waveform analysis has any
clinical value in the prediction of pre-eclampsia,
intrauterine growth retardation and perinatal death. We
also investigated whether any inconsistencies in the
results between the various studies (heterogeneity) can
be explained by differences in study quality, Doppler
scanning techniques and gestational age at scanning.
METHODS
The systematic review was based on a prospective pro-
tocol designed to address the above questions. Initially,
two of us (A.G. and P.O.) independently conducted com-
puterised MEDLINE searches (January 1966-January
1997) with the following search strategies: the first
search was conducted with the term pregnancy in the
title, abstract or medical subject heading (MeSH), com-
bined with uterine or uteroplacental and Doppler as
textwords and limited to human studies; the second
search utilised the term pregnancy in Thesaurus,
exploding it to include all subheadings, then combining
it with the textwords uterine and Doppler and again lim-
ited to human studies. We used two independent elec-
tronic search strategies in order to maximise the number
of published articles identified for the overview. The
citation list in each search, containing only the titles,
MeSH headings and abstracts (where available), was
independently reviewed by two authors (A.G. and P.O.)
who were blinded to information on the authors names,
their institutional affiliation, the publication language,
the year of publication and the name of the journal. For
inclusion in the overview, objective criteria were chosen
for the study population, the diagnostic intervention and
the outcome measure(s). Each citation was therefore
deemed to be relevant or not relevant depending on
whether it satisfied all the preset criteria. For both the
searches, the complete manuscripts of all the citations
considered relevant by the reviewer were then retrieved.
We also supplemented the citation list from the elec-
tronic search with pertinent citations obtained from
scanning of reference lists of all primary and review
articles and reviews of recent journal issues not covered
by the search. Any known unpublished studies were also
included into the overview.
The eligibility of all the English language articles was
independently assessed by two of us (P.C. and N.A.) by
review of the entire manuscript under masked conditions
(i.e. the names and affliations of the authors, the date of
publication, the journals name and the sources of finan-
cial support were concealed in the manuscript). Any dis-
agreement was resolved by consensus or arbitration by a
third reviewer (A.G.). The review of articles published in
non-English languages was performed by reviewers with
medical training who comprehended the language.
In situations where there was suspicion of duplication
in the reporting of data, the first authors of these articles
were contacted to clarify the uncertainty. In the event
that there was partial duplication of reporting of data,
the article with the larger sample size was included in
the overview.
The following criteria were used to select articles
from the electronic database for full scrutiny of their
entire manuscript:
1. Population: Pregnant women, both at low or high risk
2.
3.
of -developing hypertensive disorders and related
complications.
Diagnostic intervention: Antenatal uterine artery
Doppler flow velocimetry, conducted during second
or third trimester of pregnancy including continuous
wave and pulsed wave Doppler scanning, and colour
flow mapping.
Outcome measures: Pre-eclampsia, intrauterine I
growth retardation and perinatal death.
Methodological quality criteria
Methodological quality of all the English language arti-
cles was assessed by two of us independently (PC. and
N.A.). The following criteria for methodological quality
assessment were chosen based on the belief that they con-
tribute to the internal validity of a diagnostic test study?
1. Population: For the method of sampling of the study
population, consecutive recruitment of eligible women
was considered to be ideal. Convenience sampling,
(i.e. arbitraq recruitment or nonconsecutive recruit-
ment) was deemed to be inadequate. In the absence of
any explicit information in the manuscript on the
method of recruitment, the article was categorised as
having unclearly reported population enrolment.
0 RCOG 2000 BJOG 107.196-208
198 P. F. W. CHI EN ET A L .
2. Diagnostic intervention: The description of the uter-
ine artery Doppler velocity waveform analysis was
considered to be ideal if the scanning method (i.e.
whether continuous wave, pulsed wave, colour map-
ping, transabdominal or transvaginal scanning was
used) was reported together with the gestational age
at the time of Doppler scanning, the measurement
parameter used and the cutoff level for an abnormal
result. In the absence of any of the above information
in the manuscript, then the diagnostic intervention
was considered to be unclearly reported.
3. Outcome measures: Blinding of the outcome mea-
sure from the results of the Doppler velocimetry was
considered ideal if it was clearly reported that the
attending clinicians managing the subjects were kept
unaware of the results of the Doppler findings. If the
results of the Doppler recordings were divulged to
the attending clinicians, then blinding was cate-
gorised to be inadequate. In the absence of any such
reporting, blinding was considered to be unclearly
reported. Information on the number of women
recruited into the study and those whose outcome
data were known was also sought from the
manuscripts. Women whose outcomes were deleted
from data analysis on the basis of fetal anomalies,
multiple pregnancies, spontaneous abortion and
scanning performed out with the specified gestational
limits were considered to be legitimate exclusions.
Withdrawal of women from the study, missing data
and lack of outcome data due to delivery out with the
hospital in which the study was conducted were cate-
gorised as lost to follow up. Follow up was consid-
ered to be ideal if >90% of the women originally
enrolled into the study without legitimate exclusions
were included in the data analysis. If data from only
81%-90% of the recruited women were available for
analysis, then it was classified as second best. Follow
up was defined as inadequate when data from 2 80%
of enrolled women were available for analysis.
Data extraction
Two authors (P.C. and N.A.) independently extracted
information from each article in order to construct 2 x 2
tables of the diagnostic test result and pregnancy out-
comes. Any disagreement was resolved by conference.
In order to reduce heterogeneity in the results, the tar-
get population of pregnant women was subdivided into
those with low or high risk pregnancies. The assignment
of the selected studies into these subgroups was per-
formed by the authors of the original studies and it was
confirmed independently by two of us (P.C. and N.A.).
Studies which recruited an unselected obstetric popula-
tion with normal pregnancies at the time of Doppler
assessment were categorised as having low risk subjects.
Pregnant women with advanced age (2 35 years), previ-
ous poor pregnancy outcome, vascular complications
during previous pregnancies, previous small for gesta-
tional age babies, insulin-dependent or gestational dia-
betes mellitus, essential hypertension, previous severe
pre-eclampsia, systemic lupus erythematosus, antiphos-
pholipid syndrome, renal disease, unexplained elevated
maternal serum a-fetoprotein were classified into the
high risk population.
The diagnostic test result was also further stratified
according to type of ultrasound scanning employed
(transabdominal or transvaginal) and whether the mea-
surement parameter was based on flow velocity wave-
form ratio f diastolic notch or the presence or absence
of a diastolic notch alone. The test result was considered
to be abnormal if the diastolic notch was present in the
velocity waveform of one or both uterine arteries.
Outcome data on pre-eclampsia, intrauterine growth
retardation and perinatal death was recorded where
available. We set a priori that the criteria for pre-
eclampsia should include the presence of both hyperten-
sion and proteinuria. The definition of hypertension
utilised by the selected studies included blood pressure
2 140/90 mmHg on two occasions which were more
than 4 hours apart, a single reading of diastolic blood
pressure 2 110 mmHg or a rise in blood pressure
2 30/15 mmHg on two occasions which were more than
4 hours apart. Significant proteinuria was considered to
be present when more than 150-500 mg of protein was
excreted per 24 hours or 1 1+on labstix testing of the
urine specimen. Intrauterine growth retardation was
defined as infant birthweight c 10th centile for gesta-
tional age. Perinatal death included all intrauterine
deaths beyond fetal viability and neonatal deaths during
the first week of postnatal life.
Data analysis
To assess the reproducibility of study selection and
methodological quality assessment, we evaluated the
agreement between the two reviewers using percentage
agreement and weighted kappa statistics'. Substantial
reviewer agreement was considered to be present when
the kappa levels were >0.65'O.
The main analysis was restricted to all studies in
which 2 x 2 tables of the diagnostic test results and the
relevant pregnancy outcomes could be extracted. The
summary receiver-operator characteristic curve is still
considered the preferred method of pooling dichoto-
mous test result from primary studies'. Because there
was considerable differences in the cutoff level for
abnormality used in the subgroup of studies that utilised
flow velocity waveform ratio 2 diastolic notch as the
measurement parameter, we initially tested for a high
positive correlation (i.e. correlation coefficient >0.6)
0 RCOG 2000 BJOG 107.196-208
UTERI NE ARTERY DOPPLER FLOW VEL OCI METRY 199
between their true positive rates and the false negative
rates using the Spearman correlation test to determine
if a summary receiver-operator characteristic curve
could be generated". Since none of the relevant sub-
group of studies generated a sufficiently high positive
correlation, we then conducted our analyses using
likelihood ratio as the measure of diagnostic attribute
of a test.
Heterogeneity of results between different studies
was formally assessed using the Breslow-Day test12
which compared the ratio of the odds of having the out-
come of interest when the test result was positive to the
odds of having the same outcome with a negative test
result for each study. If significant heterogeneity was
present, we explored for the potential sources of it by
further stratifying the relevant studies according to vari-
ation in methodological quality (ideal versus inadequate
or unclearly reported studies), method of Doppler ana-
lysis (continuous wave versus pulsed wave Doppler
scanning) and gestational age of scanning (scans per-
formed at 16-24 weeks of gestation versus >24 weeks
of gestation) for sensitivity analyseP.
Pooling of likelihood ratios was performed for prede-
fined subgroups of study populations subject to the use
of either uterine artery flow velocity waveform
ratios f diastolic notch or diastolic notch alone as the
manner of determining test abnormality. For the purpose
of meta-analysis, we weighted the log (likelihood ratio)
from each study in inverse proportion to its variance in
order to combine the likelihood ratios from each study.
All the methods for data analysis used in this overview
have been reported previously by us elsewhere14. The
interpretation of likelihood ratios for positive and nega-
tive test results has been reported by J aeschke et ~ 1 . ' ~ . A
likelihood ratio of 1 indicated that the test has no predic-
tive value for the outcome of interest. In order for con-
clusive prediction of the outcome event of interest to be
achieved, a likelihood ratio of >10 or <0.1 would be
required for a positive and negative test result, respec-
tively. Moderate prediction can be achieved with likeli-
hood ratio values of 5-10 and 0.1-0-2 whereas
likelihood ratios of 1-5 and 0.2-1 would generate only
minimal prediction.
To demonstrate the practical application of the likeli-
hood ratios generated, we calculated post-test probabili-
ties for the various pregnancy outcomes by using Bayes'
theorem. An estimate of the pre-test probability was
obtained by calculating the prevalence of the outcome
event in the population studied. The algorithm of equa-
tions used for calculating post-test probability and the
95% confidence interval around the point estimate have
also previously been reported by us14- In the same man-
ner, clinicians can also use the likelihood ratios gener-
ated from here to calculate the post-test probabilities of
the relevant pregnancy outcomes based on the preva-
lence rates of their own practice population. The clinical
usefulness of the test can therefore be assessed for dif-
ferent practice populations with the result of enhancing
the external validity of the overview.
RESULTS
The initial two independent MEDLIIW searches by
A.G. and P.O. yielded 501 and 479 citations, respec-
tively. After blinded scrutiny of the titles and abstracts
of these articles by the two independent reviewers, there
were 46 articles which both reviewers thought were rel-
evant and four articles which at least one of the review-
ers considered to be relevant. All these four articles were
identified by both searches. The complete manuscripts
of all these articles considered relevant by any of the
reviewers were then retrieved for further assessment. Of
the 50 articles, 45 were published in English, two in
German and one each in French, Portuguese and
J apanese. Twenty-two further articles (20 published in
English, one in French and one known unpublished
study) were identified through examining the bibliogra-
phy of known primary and review articles or obtained
from personal files maintained through the constant
searching of recent issues of journals addressing obstet-
ric issues.
After independent review of the English manuscripts
under masked conditions, 30 articles6*'- were consid-
ered to be eligible to be included in the overview. The
agreement concerning eligibility was 92% (kappa 0-85).
The five instances of disagreement were due to an over-
sight of one of the reviewers with regards to appropri-
ateness of the study population (one article) and
relevance of the reported outcome data (four articles).
The disagreement was easily resolved by conference.
The reasons for the remaining 42 articles to be excluded
were inappropriate study design (1 1 articles), inappro-
priate study population (nine articles), lack of clarity of
the cutoff level for abnormal test result (one article) and
outcome measure (one unpublished article), and lack of
relevant outcome data reported (twenty articles). The
bibliography of the articles which were considered to be
ineligible for inclusion into the systematic review can be
obtained from the authors.
Following the assessment of eligibility, there were
four article^^.'^^"^^in which partial duplication of data
reporting was suspected. Two of these6*18 were excluded
from the overview when the first authors of these articles
confirmed that the data had been reported elsewhere.
Thus, 28 article^'"'^.'^ were included into the
overview; pre-eclampsia was reported in 22 studies
( 7 9 ~ ~ ) 1 6 1 7 , 1 9 - 2 0 . 2 2 - ~ ~ 7 , 2 &3 3 , ~ 6 3 8 . ~ 2 . ~ ,
retardation was reported in 24 studies (86%)'617,2'-23,25,27-44
and eight studies (28%)17,2325-26,28,"*3637 repofled on peri-
natal death (Table l). Of the eight articles that reported
0 RCOG 2000 BJOG 107,196-208
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W

UTERI NE ARTERY DOPPLER FLOW VEL OCI METRY 201
on perinatal death, the gestational age for fetal viability
was defined as 24 weeks of gestation in one study36,
18-22 weeks of gestation in another study17 and unde-
fined in the remaining studies23,25-26,28.31~37. Sixteen of
provided data on
low risk obstetric populations whereas twelve arti-
reported on antenatal women who
were considered to be at high risk of developing antena-
tal complications.
these articles 1647,2&2 13.27.33-37.39.4 1-44
c1es19,22-24,26,28-32,38,40
Study quality
The reviewer agreement regarding the various com-
ponents of study quality varied between 68% to
100%; kappa values were 0-48 for enrolment of study
population; 0.85 for nature of study population, 0.94
for description of scanning method, 1.0 for descrip-
tion of measurement parameter used, 0.93 for
description of cutoff level for abnormal flow wave-
form ratios, the presence or absence of a diastolic
notch for test result and blinding of test results and
0.68 for follow up.
On reviewing the entire manuscripts of the 28 studies
selected for overview, there were two article^'^*^^that
reported on the same study population but different
measurement parameters (i.e. flow velocity waveform
ratio f diastolic notch and the presence or absence of a
diastolic notch alone) were used to report the data. To
avoid duplication, we have therefore excluded the latter
articleZo in the assessment of methodological qualities
(Table 2).
In the low risk population the method of population
enrolment was ideal (consecutive) in four out of 15
(100%) provided an adequate description of the uterine
artery Doppler velocity waveform analysis. Eleven
ing of test results and follow up was >90% in 11stud-
ies 16.2I .27,33-35,37,41,424l (73%). Among the 12
studies 19,22-24.26.28-32.38.40 in the high risk population, there
were two st~di es~~~ (17%) with consecutive enrolment.
Only eight studies9,224,26,29-30,38,40 (67%) provided an
adequate description of the test. Adequate blinding of
test results was present in five studies9~24~26~29~40 (42%)
and follow up was >90% in 11 stUdies19.22-23,26,28-32,38,40
(92%).
risk population, the uterine artery Doppler velocity
waveform analysis was performed using transabdomi-
nal ultrasound in all except for one study4]. This study4
utilised transvaginal scanning for Doppler analysis and
hence was excluded from meta-analyses. Doppler
velocimetry in all the 12 stUdies19~22-24~26~28-32~38~40 in the
high risk population were performed with the trans-
abdominal approach.
studies 16-17.25.39 (27%). All 15 studies117.21.25.27.3337,39.41~4
StudieS1~17. 21. 25. 27, 3~35, 37, 39, 42. ~ (73%) had adequate blind-
Among the 15 st~di es~7. 21. 25. 27. 33-37. 39. 41~4 in the low
Table 2. Methodological quality of uterine artery Doppler ultrasound
studies included in overview. Values are given as d n (%).
Low risk* High risk
Quality criteria population population TOTAL
Population
Enrolment
Ideal (consecutive) 4/15 (26.7) 2/12 (16.7) 6/27 (22.2)
Inadequate (arbitrary) 1/15 (6.7) 2/12 (16.7) 3/27 (11.1)
Unclearly reported 10/15 (66.6) 8/12 (66.6) 18/27 (66.7)
Diagnostic test
Description of scanning
method, gestation at scan,
measurementparameter
and cutoff level
Ideal 15/15 (100) 8/12 (66.7) 23/27 (85.2)
Unclearly reported 0115(0) 4/12 (33-3) 4/27 (14.8)
Outcome
Blinding of results
Ideal 11/15 (73.3) 5/12 (41.7) 16/27 (59.2)
Inadequate 0/15 (0) 1/12 (8.3) 1/27 (3.7)
Unclearly reported 4/15 (26.7) 6/12 (50.0) 10/27 (37.1)
Follow up
Ideal (>90%) 11/15 (73.3) 11/12 (91.7) 22/27 (81.5)
Second best (81-90) 3/15 (20.0) 1/12 (8.3) 4/27 (14.8)
Inadequate (S 80%) 1/15 (6.7) 0112(0) 1/27 (3.7)
*Two
Doppler measurement parameters and hence the assessment of
methodological quality was not duplicated on them.
reported on the same population with different
Uterine artery Doppler ultrasound in low risk
population
meta-analyses in the low risk population. The likelihood
ratios generated for the different measurement parame-
ters and outcomes produced minimal to moderate shift
in pre-test to post-test probabilities (Tables 3 and 4).
The use of an abnormal velocity waveform ratio f the
presence of a diastolic notch to predict pre-eclampsia
resulted in a heterogeneous estimate of likelihood ratios:
6-4 (95% CI 5.7-7.1) for a positive test result and 0.7
(95% CI 0.6-0-8) for a negative test result (Breslow-
Day test, P =0.0001). Exploration of the sources of het-
erogeneity by performing sensitivity analyses on studies
subgroups based on the various features of methodolog-
ical quality and types of Doppler scanning techniques
used could not provide an adequate explanation. In gen-
eral, studies with adequate methods generated more
conservative estimates of diagnostic prediction but the
confidence intervals in the subgroups overlapped
(Table 5) . Pulsed wave Doppler scanning also produced
more conservative estimates of likelihood ratio for a
positive test result but a more liberal estimate of likeli-
hood ratio was obtained with a negative test result
(Table 5) . Furthermore, the exclusion of studies with
nonadequate methods and those that only employed
There were
15 articles1~17,20-21.25.27.3-37.39,42~4 used for
0 RCOG 2000 BJOG 107,196-208
202 P. F. W. CHIEN ETAL.
Table 3. Likelihood ratios for predicting pre-eclampsia, intrauterine growth retardation and perinatal death in primary studies of uterine artery
Doppler ultrasound on low risk population. LR =likelihood ratio; IUGR =intrauterine growth retardation.
Cutoff level for test and
outcome measure
Positive test Negative test
n/n (%) LR (95% CI)* n/n (%) LR (95% CI)*
Flow waveform
ratio f diastolic notch
Pre-eclampsia
Campbell et al. (1986)
Steel et al. (1990)37
Bewley et al. (1991)16
Bower et al. (1993)17
Valensise et al. (1993)33
North et al. ( 1994y7
Harrington et al. (1996)36
Frusca et al. (1997)42
Irion et al. ( 1998)44
Campbell et al. (1986)25
Schulman et al. (1987)34
Hanretty et al. (1989)9
Newnhamet al. (1 990)
Steel et al. (1 990)7
Bewley et al. (1991)16
Bower et al. (1993)
Valensise et al. (1993)33
North et al. (1994)27
Todros et al. (1995)21
Hanington et al. (1996y6
Frusca et al. (1997r2
Liberati et al. (1997)43
Irion et al. (1998)44
Campbell et al. (1986)
Steel etal. (1990)37
Bower e f al. (1993)17
Harrington ef al. (1996)36
IUGR
Perinatal death
Diastolic notch alone
Pre-eclampsia
Bower et al. (1993)20
Hanington et al. (1996)3b
Irion et al. (1998)
Harrington et al. (1996)36
Irion et al. (1998)44
IUGR
9/50 (18.0)
27/118 (22.9)
10/51 (19.6)
39/329 (1 1.8)
8/26 (30.8)
34/110 (30.9)
7/36 (19.4)
12/118 (10.2)
12/50 (24.0)
6/16 (37.5)
1/19 (5.2)
3/24 (1 2.5)
32/118 (27.1)
18/52 (34.6)
84/329 (25.5)
14/26 (534)
15/56 (26.8)+
5/59 (8.5)t
42/110 (38.2)
16/36 (44.4)
22/63 (34.9)
33/118 (28.0)
1/50 (2.0)
5/118 (4.2)
5/329 (1.5)
11110 (1.0)
4/53 (7.5)+
37/301 (12.3)
34/110 (30.9)
12/160 (7.5)t
42/110 (38.2)
38/160 (23.8)
1.8 (1.1-2.8)
8.6 (7.3-9.1)
5.1 (2.7-9.4)
5.2 (4.3-6.3)
13.0 (7.9-21.5)
2.4 (1.0-5.6)
11.8 (9.0-15.4)
9.0 (5.1-15.8)
2.7 (1 6-4.6)
1.9 (1.2-2.9)
3.3 (1.5-7.2)
1.0 (0.1-6.7)
1.3 (0.443)
3.5 (2.5-5.0)
3.6 (2.1-6.1)
2.8 (2.3-3.4)
13.9 (7.4-26.2)
5.2 (3.3-8.3)
1.9 (0.84.6)
5.1 (3.6-7.1)
9.4 (5.4-16.3)
4.8 (3.1-7.4)
3.2 (2.2-4.5)
1.9 (0.844)
3.0 (1.4-6.2)
1.2 (0.5-2.6)
0.9 (0.1-6.0)
6.3 (5.3-7.5)
11.8 (9.0-15.4)
2.0 (1.2-3.3)
5.1 (3.6-7.1)
2.5 (1.8-3.5)
5/76 (6.6)
7/896 (0.8)
32/866 (3.7)
13/1729 (0.8)
1/246 (0.4)
11/393 (2.8)
10/1094 (0.9)
4/383 (1.0)
34/1041 (3.3)
6/76 (7.9)
5/55 (9.1)
15/272 (5.5)
46/477 (9.6)
65/896 (7.2)
100/861 (1 1.6)
141/1729 (8.2)
7/246 (2.8)
15/401 (3.7)t
37/857 (4.3)
89/1094 (8.1)
17/383 (4.4)
28/436 (6.4)
94/947 (9.9y
0/76 (0)
101896 (1.1)
22/1729 (1.3)
11/1094 (1.0)
8/1757 (0.4)
10/1094 (0.9)
34/999 (3.4)t
89/1094 (0.1)
891999 (8.9)
0.6 (0.3-1.2)
0.2 (0.1-0.4)
0.8 (0.7-0.9)
0.3 (0.24.5)
0.1 (0.02-0.8)
0.8 (0.6-1.1)
0.2 (0.144)
0.4 (0.2-0.8)
0.8 (0.7-1.0)
0.5 (0.3-1.0)
0.5 (0.3-1.0)
1.0 (0.9-1.1)
1.0 (0.9-1.1)
0.7 (0.6-0.8)
0.9 (0.8-1.0)
0.7 (0.64.8)
0.4 (0,246)
0.6 (0-4-0.8)
0.9 (0.8-1.0)
0.7 (0.6-0.8)
0-5 (044.8)
0.6 (0.5-0.8)
0.8 (0.7-0.9)
0.4 (0.04-4.6)
0.8 (0.5-1.1)
1 .O (0.8-1.2)
1 .o (04-1.2)
0.2 (0.14.4)
0.2 (0.144)
0.8 (0.7-1 .O)
0.7 (0.648)
0.8 (0.7-0.9)
*In the presence of zero in any cell of the 2 x 2 table, 0.5 was added to each cell to calculate the likelihood ratios.
Outcome data calculated from prevalence, sensitivity and specificity reported in original article.
continuous wave scanning had minimal effect on the
overall estimate. Since the ultrasound scans for all the
studies reporting on this outcome measure was con-
ducted I 24 weeks of gestation, it was not possible to
explore for sources of heterogeneity based on the gesta-
tional age of ultrasound scanning.
The likelihood ratios generated for the prediction of
intrauterine growth retardation were also heteroge-
neous: 3.6 (95% CI 3.240) for a positive test result and
0.8 (95% CI 0-8-0.9) for a negative test result. Again,
the sources of heterogeneity remained unexplained after
performing sensitivity analyses on the various study
subgroups. The likelihood ratios remained virtually
unchanged irrespective of the methodological quality of
the studies, method of Doppler scanning employed for
screening for this outcome and gestational age of scan-
ning (Table 5).
For the prediction of perinatal death, the pooled like-
lihood ratio was 1-8 (95% CI 1.2-2.9) and 0.9 (95% CI
0.8-1.1) for positive and negative test results, respec-
tively. Consequently, the pre-test probability given a
positive test result was only minimally increased from
0 RCOG 2000 BJOG 107,196-208
UTERINE ARTERY DOPPLER FLOW VELOClMETRY 203
Table 4. Pooled estimates of pre-test probabilities, likelihood ratios and post-test probabilities for uterine artery Doppler ultrasound in
predicting pre-eclampsia, intrauterine growth retardation and perinatal death. IUGR =intrauterine growth retardation.
Pre-test
probability
% (95% CI)
Likelihood
ratio
(95% CI)
Post-test
probability
% (95% CI)
Population, cutoff level
for test and outcome measure
LOW RISK POPULATION
Flow waveform
Pre-eclampsia (n =9 studies)
ratio i diastolic notch
Positive test result
Negative test result
IUGR (n =14 studies)
Positive test result
Negative test result
Positive test result
Negative test result
Diastolic notch alone
Pre-eclampsia (n =3 studies)
Positive test result
Negative test result
IUGR (n =2 studies)
Positive test result
Negative test result
Perinatal death (n =4 studies)
3.5 (3.1-3.9)
3.5 (3.1-3.9)
6.4 (5.7-7.1)*
0.7 (0.6-0.8)*
18.8 (164-21.5)
2.5 (2.1-2.9)
9.8 (9-2-10.4)
9.8 (9.2-10.4)
3.6 (3.240)*
0-8 (0.8-0-9)*
28-0 (25430.7)
8.4 (7-8-9.0)
1.3 (0.9-1.6)
1.3 (0.9-1.6)
1.8 (1.2-2.9)
0.9 (0.8-1.1)
2.3 (14-3.8)
1.2 (0.9-1.6)
3.0 (2.5-3.6)
3.0 (2.5-3.6)
6.8 (5.9-7.9)*
0.7 (0.648)*
3.5 (2.844)**
0.8 (0.748)**
17.7 (14.7-21.2)
2.2 (1.7-2.7)
29.9 (24.7-35.7)
8.5 (7.4-9.8)
10.9 (9.7-12.2)
10.9 (9.7-12.2)
HIGH RISK POPULATION
Flow waveform
Pre-eclampsia (n =11 studies)
ratio f diastolic notch
Positive test result
Negative test result
IUGR (n =9 studies)
Positive test result
Negative test result
Positive test result
Negative test result
Diastolic notch alone
Pre-eclampsia (n =1 study)
Positive test result
Negative test result
Positive test result
Negative test result
Positive test result
Negative test result
Perinatal death (n =4 studies)
IUGR (n =1 study)
Perinatal death (n =1 study)
9.8 (74-11-8)
9.8 (7-9-1 1-8)
17.8 (144-21.1)
17.8 (14.4-21.1)
2.8 (2.3-3.4)
0.8 (0.749)
23-5 (186-29.2)
7-8 (6.1-10.0)
2.7 (2.1-3.4)
0.7 (0.649)
36.7 (29.5-44.6)
13.8 (10.7-17.6)
8.9 (54-12.3)
8.9 (54-12.3)
4.0 (244.6)
0.6 (0.4-0.9)
27.8 (16442.9)
5.5 (3.1-9.7)
5.8 (1.3-10.3)
5.8 (1.3-10.3)
20-2 (7.3-56-3)
0.2 (0.03-1.0)
55.6 (25.1-82.3)
1.1 (0.1-7.2)
17.5 (10.1-24.8)
17.5 (10.1-24.8)
1.9 (0.7-4.5)
1.9 (0.745)
2.4 (06-8.6)
0.9 (0.7-1.1)
2.7 (0.2-32.2)
0.8 ( 041. 8)
33.3 (11.1-66-6)
16.0 (9.9-24.7)
5.0 (0.3-47.5)
1.6 (0-3-7-4)
Heterogeneity: *P <0.0001, **P <0.05; results homogenous for other meta-analyses; Breslow-Day test used.
1.3% (95% CI 0*9-1*6%) to 2.3% (95% CI 1*4-3.8%).
With a negative test result, it only decreased to 1.2%
(95% CI 0.9-1.6%). The pooled estimates of likeli-
hood ratio for the prediction of perinatal death were
homogeneous.
Data from the studies with test results based on the
presence or absence of a diastolic notch alone only
reported for pre-eclampsia and intrauterine growth retar-
dation. The pre-test probability of pre-eclampsia was
3.0% (95% CI 2.5-3.6%). A positive result generated
moderate shift in the pre-test probability; the pooled
likelihood ratio for a positive test result was 643(95% CI
5.9-7-9), raising the probability to 17.7% (95% CI
14-7-21.2%). A negative test result had a minimal
effect; the pooled likelihood ratio was 0.7 (95% CI
0&0.8), reducing the probability to 2.2% (95% CI
1.7-2.7%). For intrauterine growth retardation, the
pooled likelihood ratio for a positive test result was 3.5
(95% CI 2.844) and 0.8 (95% CI 0-7-0.8) for a nega-
tive test result. There was only a minimal increase in the
0 RCOG 2000 BJOG 107,196-208
204 P. F. W. CHIEN ET AL.
pre-test probability from 10.9% (95% CI 9.7-12.2%) to
29.9% (95% CI 24.7-357%) with a positive test result.
It decreased only to 8.5% (95% CI 749.8%) with a
negative test result. However, the pooled estimates of
likelihood ratio in all these analyses were heteroge-
neous. Since the methodological quality of all the stud-
ies with test results based on the presence or absence of
a diastolic notch alone were nonideal and employed
pulsed wave Doppler scanning before 24 weeks of ges-
tation, the exploration for the sources of heterogeneity
was not possible with the meta-analyses based on both
these two outcome measures.
Uterine artery Doppler ultrasound in high risk
population
Twelve of the eligible s t ~ d i e s ' ~ ~ ~ ~ - ~ ~ ~ ~ ~ ~ ~ ~ - ~ ~ ~ ~ ~ ~ ~ ~ were cate-
gorised as having recruited high risk subjects (Table 6).
The pooled likelihood ratios from all the analyses in the
high risk subgroup were homogeneous (Table 4).
When the presence of an abnormal velocity wave-
form ratio & diastolic notch was used to predict pre-
eclampsia, the likelihood ratios generated were 2.8
(95% CI 2-3-3.4) and 0.8 (95% CI 0-7-0.9) for a posi-
tive and negative test result, respectively. The pre-test
probability for this outcome was 9.8% (95% CI
7.9-1 1.8%). These likelihood ratios resulted in minimal
increase in the pre-test probability to 23.5% (95% CI
18.6-29.2%) for a positive test result and decrease to
7.8% (95% CI 6-1-10.0%) for a negative test result. For
intrauterine growth retardation, the pooled likelihood
ratios were similarly disappointing; 2.7 (95% CI
2.1-3-4) for a positive test result and 0.7 (95% CI
0-6-0.9) for a negative test result. The pre-test probabil-
ity increased from 17.8% (95% CI 14.4-21.1%) to
36.7% (95% CI 29~544.6%) with a positive test result.
It decreased to 13.8% (95% CI 10.7-17.6%) in the pres-
ence of a negative test result. The pooled likelihood
ratios for the prediction of perinatal death were 4.0
(95% CI 2.4-6-6) and 0.6 (95% CI 0.4-0-9) for a posi-
tive and negative test result, respectively. A positive test
result increased the pre-test probability from 8.9% (95%
CI 5412.3%) to 27.8% (95% CI 16-4-42-9%), whereas
it is decreased to 5.5% (95% CI 3.1-9.7%) with a nega-
tive test result.
There was only one study28 that used the presence or
absence of a diastolic notch as the measurement param-
eter and hence pooling of results was not possible. The
pre-test probability for pre-eclampsia was 5.8% (95%
CI 1.3-10.3%). The likelihood ratio for a positive result
was 20.2 (95% CI 7-3-56.3), resulting in a large change
in pre-test probability to 55.6% (95% CI 25.1-82-3%).
A negative test result generated a moderate shift in pre-
test probability; likelihood ratio was 0.2 (95% CI
0-03-1.0), resulting in a post-test probability of 1.1%
Table 5. Sensitivity analysis of meta-analyses of uterine artery
Doppler ultrasound using flow velocity waveform ratio f diastolic
notch as measurement parameter in low risk population.
Likelihood ratio (95% CI)
Outcome criteria (no. of studies) Positive test Negative test
Pre-eclampsia
Study quality*
Ideal (n =1) 5.1 (2.7-9.4) 0.8 (0.7-1.0)
Inadequate/unclearly reported (n =8) 6.4 (5.7-7.2) 0.5 (040.6)
All studies (n =9) 6.4 (5.7-7.1) 0.7 (0.648)
Doppler scanning method
Continuous wave Doppler (n =2)
Pulsed wave Doppler f color flow
7.9 (6.2-10.0) 0.7 ( 064. 9)
mapping (n =7) 6.3 (5.5-7.2) 0.5 (0.4-0.6)
All studies (n =9) 6.4 (5.7-7.1) 0.7 (0.6-0.8)
Gestational age of scanning
Scan I 2 4 weeks of gestation (n =9) 6.4 (5.7-7.1) 0.7 (06-0.8)
Scan >24 weeks of gestation (n =0)
- -
All studies (n =9) 6.4 (5.7-7.1) 0.7 (0.6-0.8)
I ntrauterine growth retardation
Study quality*
Ideal (n =1) 3.6 (2.1-6.1) 0.9 (0.8-1.0)
All studies (n =14) 3.6 (3.240) 0.8 (0.8-0.9)
Inadequate/unclearly reported (n =13) 3.6 (3,240) 0.8 ( 0&0. 9)
Doppler scanning method
Continuous wave Doppler (n =5) 3-2 (2.542) 0.9 (09-1.0)
Pulsed wave Doppler k color flow
mapping (n =9) 3.7 (3.242) 0.8 (0.7-0.8)
All studies (n =14) 3.6 (3.240) 0.8 (0.8-0.9)
Gestational age of scanning
Scan I 2 4 weeks of gestation (n =12) 3.6 (3.2-4.0) 0.8 ( 0, 849)
Scan >24 weeks of gestation (n =2) 2.8 (1.3-5.7) 1.0 (0.9-1.1)
All studies (n =14) 3.6 (3.240) 0.8 (0.8-0.9)
*Study quality was considered to be ideal when consecutive
enrollment of study population was employed, a description of the
gestational age at the time of Doppler scanning, themeasurement
parameter used and the cutoff level for an abnormal result was
provided in the manuscript, Doppler results was adequately blinded to
the attending physicians and >90% of all the women enrolled into the
study were available for data analysis. All other methods of study
design for the population enrollment, diagnostic intervention used and
ascertaining the outcome measure(s) were considered inadequate. In
the absence of any explicit information on the above methodological
quality, the study was classified as unclearly reported.
(95% CI 0.1-7.2%). The limited sample size in this ana-
lysis resulted in the upper limit of the estimate of likeli-
hood ratio for a negative test result to include unity,
producing a considerable amount of uncertainty around
it. There was limited prediction for intrauterine growth
retardation; the likelihood ratios were 2.4 (95% CI
06-8.6) and 0.9 (95% CI 0.7-1.1) for a positive and
negative test, respectively. The pre-test probability
therefore increased from 17.5% (95% CI 10.1-24.8%)
to 33.3% (95% CI 11-1-66-6%). It decreased to 16.0%
(95% CI 9.9-24.7%) with a negative test result. For peri-
natal death, the likelihood ratio was 2.7 (95% CI 0.2-32.2)
for a positive test result and 0.8 (95% CI 04-1.8) for a
0 RCOG 2000 BJOG 107,196-208
UTERI NE ARTERY DOPPLER FLOW VEL OCI METRY 205
Table 6. Likelihood ratios for predicting pre-eclampsia, intrauterine growth retardation and perinatal death in primary studies of uterine artery
Doppler ultrasound on high risk population. LR =likelihood ratio; IUGR =intrauterine growth retardation.
Positive test Negative test
Cutoff level for test and
outcome measure dn (%) LR (95% CI)* dn (%b) LR (95% CI)*
Flow waveform
ratio i diastolic notch
Pre-eclampsia
Trudinger et a/. (1985)32
Jacobson et a/ . (1990)40
Pattinson et a/ . (1991)19
Benifla et al. (1992)38
Guzman et a/ . (1992)3
Caruso et al. (1993)23
Haddad et a/ . (1993)22
Femer et a/. (1994)29
Chan eta/. (1995)24
Haddad et a/. ( 1995y0
Konchak et a1. (1995)28
Trudinger et a/. (1985)
Jacobson et a/ . (1990)40
Benifla et al. (1992)38
Guzman et al. (1992)31
Caruso et al. (1993)
Haddad et al. (1993)22
Femer et al. ( 1994y9
Haddad et al. (1995)
Konchak et a/ . (1995)*
Aristidou et a/. (1990p
Guzman et al. (1992)3
Caruso et al. (1993)23
Konchak et a/. (1995)28
IUGR
Perinatal death
Diastolic notch alone
Pre-eclampsia
IUGR
Perinatal death
Konchak et a/ . (1995)
Konchak et a/ . (1995)28
Konchak eta/. (1995)
9/28 (32.1)
6/36 (16.7)t
6/20 (30.0)
4/6 (66.7)
2/4 (50.0)
4/8 (50.0)
215(40.0)
2/14 (14.3)
4/18 (22*2)+
5/26 (19.2)
5/11 (45.4)
15/28 (53.6)
12/36 (33.3)+
5/10 (50.0)
4/4 (loo)
2/7 (28.6)
215(40.0)
5/14 (35.7)
4/26 (15.4)
3/11 (27.3)
7/18 (38.9)
3/4 (75.0)
2l8 (25.0)
0/11 (0)
519(55.6)
319(33.3)
0/9 (0)
3.1 (1.9-5.2)
1.8 (1.1-3.1)
2.8 (1.7-4.8)
3.5 (1.7-7.1)
2.4 (04-14.0)
4.0 (1.5-10.7)
8.6 (2.8-26.2)
2.0 (0.7-5.8)
3.9 (14-10.8)
1.9 (1.3-2.8)
13.5 (5.7-31.6)
3.0 (1.7-5.5)
2.2 (1.4-3.4)
4.0 (1.8-8.7)
28.3 (1.7463.0)
2.9 (1.0-8.9)
8.6 (2.8-26.2)
4.2 (2.1-8.3)
1.6 (0.9-2.6)
1.8 ( 0. 540)
3.8 (1.8-8.2)
14.6 (34-71.9)
3.1 (1.3-7.0)
2.2 (0.2-26.2)
20.2 (7.3-56.3)
2.4 (06-8.6)
2.7 (0.2-32.2)
3/63 (4.8)
3/55 (5.4)
1/33 (3.1)
6/23 (26.1)
1/17 (5.9)
2/37 (5.4)
191316 (6.0)
0122(0)
1/92 (1.1)
10163 (15.9)
5/55 (9.1)
223 (8.7)
1/18 (5.6)
0132(0)
1/37 (2.7)
1/22 (4.5)
15/92 (16.3)
7/80 (8.8)
0118(0)
0132(0)
0118(0)
0123(0)
0/17 (0)
1/92 (1.1)
1/94 (1.1)
15/94 ( 16.0)
1/94 (1.1)
0.3 (0.1-0.9)
0.5 (0.2-1.3)
0.2 (0.03-1.3)
0.1 (0.01-1.9)
0.8 (0.5-1.3)
0.2 (0.041.5)
0.2 (0.01-2.3)
0.7 (0.2-1.8)
0.9 (0.7-1.0)
0.2 (0.01-2.4)
0.2 (0.03-1.1)
0.5 (0.348)
0.4 (0.2-0.9)
0.1 (0.01-1.5)
0.4 (0.1-1.0)
0.4 (0.1-2.2)
0.2 (0.01-2.3)
0.2 (0.03-1.2)
0.4 (0.1-2.4)
0.9 (0.7-1.1)
0.6 (0.3-1.0)
0.1 (0.01-1.8)
0.2 (0.02-2.9)
0.8 (04-1.9)
0.2 (0.03-1.0)
0.9 (0.7-1.1)
0.8 (04-1.8)
*In the presence of zero in any cell of the 2 x 2 table, 0.5 was added to each cell to calculate the likelihood ratios.
toutcome data calculated from prevalence, sensitivity and specificity reported in the original article.
negative test result. The pre-test probability was raised
from 1.9% (95% CI 0.745%). to 5.0% (95% CI
0.3-47.5%) with a positive test result and reduced to
1.6% (95% CI 0.3-7-4%) in the presence of a negative
test result.
DISCUSSION
In this review stringent criteria for a rigorous systematic
review were observed. Wehad a prospective protocol,
focused a priori on a research question, clearly stated
our search strategies, excluded data which were subject
to duplicate publication, assessed the study methodolog-
ical quality in an unbiased and reproducible fashion,
quantitatively summarised the evidence of diagnostic
attribute of the test, explored for heterogeneity in the
results and also for the possible sources of variation in
the data from study to studf-. Our results suggests
that an abnormal flow waveform ratio f diastolic notch
as the measurement parameter used for uterine artery
Doppler flow velocity has limited predictive value for
pre-eclampsia, intrauterine growth retardation and peri-
natal death. The presence of a diastolic notch alone as
the criterion for a positive test result in low risk popula-
tion also has limited predictive value.
It is generally agreed that pre-eclampsia should only
be diagnosed in the presence of gestational hypertension
and pr~tei nuri a~~. However, the criteria for defining
0 RCOG 2000 BJ OG 107,196-208
206 P. F. W. CHI EN ET AL .
hypertension and proteinuria is still lacking agreement.
The significant variation in the definition of hyperten-
sion and proteinuria present in the selected studies is
again another potential contributor of heterogeneity in
the results. Furthermore, other hypertensive conditions
in pregnancy such as chronic hypertension, chronic
renal disease and chronic hypertension with superim-
posed pre-eclampsia can sometimes mimic pre-eclamp-
~i a ~~. Until there is an objective reference standard to
verify the disease, we are left with no option but to rely
on this condition being diagnosed correctly by clinical
means. This problem was further compounded by the
finding that 11 out of 27 selected studies (41%) did not
adequately blind the Doppler test results from the clini-
cians who subsequently verified for the presence or
absence of disease. Not surprising, statistically signifi-
cant heterogeneity was therefore encountered in the low
risk population given that there was such significant
variation between the various studies with regards to the
criteria used to diagnose this outcome measure.
All except one of the studies selected for the overview
defined proteinuria as >300 mg per 24 hours and/or
2 2+ on labstix urine analysis. The remaining studyI6
(with exception to the above definition) considered sig-
nificant proteinuria as >150 mg per 24 hours or >1+ on
labstix testing of the urine sample. Such a level of uri-
nary protein excretion or semi-quantitative protein con-
centration may be considered to be inappropriately low
for defining significant proteinuria in pre-eclampsia4.
This study reported on the prediction of pre-eclampsia
and intrauterine growth retardation with uterine artery
Doppler velocimetry in the low risk population16. The
omission of this study16 from the meta-analyses pro-
duced pooled likelihood ratios which were virtually
identical to that presented in Table 4 (pooled likelihood
ratios were 6.4 (95% CI 5.7-7.2) for positive test result
and 0.7 (95% CI 0-6-0.7) for negative test result for pre-
eclampsia; 3-6 (95% CI 3-2-4-0) for positive test result
and 0.8 (95% CI 0.8-0.9) for negative test result for
intrauterine growth retardation). Therefore, the inclu-
sion of this study did not alter the result of the overview.
Wealso evaluated the influence of gestational age on
the uterine artery velocity waveform pattern by perform-
ing sensitivity analyses stratified according to gesta-
tional age of scanning. The physiological trophoblastic
invasion of the uterine spiral arteries occurs at 14-16
weeks of gestation48. The failure of this physiological
process is known to subsequently lead to the develop-
ment of pre-eclampsia. Hence, uterine artery Doppler
velocimetry performed before 16 weeks of gestation is
unlikely to be a useful screening test for this condition. In
addition, it is irrational to employ this test to screen for
pre-eclampsia in the third trimester of pregnancy (>24
weeks of gestation) as the disease usually would have
been established by then48. For these reasons, the studies
were dichotomised to whether the ultrasound scans were
performed between 16-24 or >24 weeks in the sensitiv-
ity analyses. All nine studies in the low risk population
with pre-eclampsia as the outcome employing screening
I 24 weeks of gestation (Table 5). With regards to the 14
studies in the same population with intrauterine growth
retardation as the outcome, the likelihood ratios for stud-
ies with Doppler ultrasound scanning at 1624 and >24
weeks of gestation were similar with overlapping confi-
dence intervals to the overall pooled likelihood ratios
(Table 5). Wehave therefore presented the result with the
overall pooled likelihood ratios in order to achieve a
more precise estimate.
The studies categorised into the high risk subgroup
included subjects with different risk factors for develop-
ing pre-eclampsia. Although a rather heterogeneous
group of conditions have been incorporated into the
meta-analyses of this subgroup, the pooled estimates of
likelihood ratios from all these analyses remained
homogenous (Table 4).
Other measures of diagnostic accuracy such as sensi-
tivity and specificity could also have been employed to
evaluate the performance of the test. These measures
lack stability when subjected to meta-analysis (i.e. sig-
nificant heterogeneity is more likely to be encoun-
tered)14s49. Moreover, inference based on sensitivity and
specificity tend to overestimate the clinical value of the
test50. In this overview we have chosen to use likelihood
ratio as our preferred measure of diagnostic accuracy
because it is independent of the prevalence of disease
and the post-test probability of disease can always be
calculated for any known pre-test pr~bability~l. Hence,
the likelihood ratios generated by this overview can be
applied to any patient population provided the preva-
lence of disease for that population is known. Because
the post-test probability refers to the probability of dis-
ease given a certain test result, it is immediately more
clinically useful to clinicians compared with sensitivity
and specificity 4s2.
Bayes theorem implies that the predictive accuracy
of any test is conditional on the overall prevalence of
disease in the population tested. The prevalence (i.e.
pre-test probability) of pre-eclampsia can be considered
low in relative terms for both the low risk (3-0%-3-5%)
and high risk (5-8%-9.8%) populations. Therefore, uter-
ine artery Doppler flow velocimetry will need to have a
high likelihood ratio in order to have a reasonable
amount of predictive ability for pre- eclampsia in the
presence of a positive test result, whereas a low likeli-
hood ratio would be required to confidently exclude the
disease with a negative test result. Unfortunately, the
likelihood ratios generated by uterine artery Doppler
waveform analysis are generally conservative, therefore
the clinical usefulness of this test in the prediction of
pre-eclampsia is limited.
0 RCOG 2000 BJOG 107,196-208
UTERI NE ARTERY DOPPLER FLOW VEL OCI METRY 207
This overview suggest that the use of uterine artery
flow waveform ratio * diastolic notch as the measure-
ment parameter for the test result has limited diagnostic
prediction for pre-eclampsia, intrauterine growth retar-
dation and perinatal death. Future research should
instead focus on Doppler ultrasonic detection of uterine
artery diastolic notches alone to predict for pre-eclamp-
sia, especially in pregnant women considered to be at
high risk for this condition. Decisions on whether to ini-
tiate medical or nonmedical interventions to prevent
pre-eclampsia should therefore not be based on these
test results alone.
Acknowledgements
The authors would like to thank Drs T. Shinomura, R.
Devlieger, M. J acobs, M. Quaresma and A. Kolle for
their contribution in extracting data from the non-
English articles.
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