How useful is uterine artery Doppler ultrasonography in predicting pre-eclampsia and intrauterine growth restriction?

Commentary
Research
How useful is uterine artery Doppler ultrasonography in
predicting pre-eclampsia and intrauterine growth restriction?
Lynne McLeod MD
@
See related article page 701
Pre-eclampsia and intrauterine growth restriction re- Key points of the article
main important causes of maternal and neonatal
complications and death.1–3 These 2 conditions are
• Pre-eclampsia and intrauterine growth restriction are im-
felt to be the result of abnormal placenta formation involv-
portant causes of maternal and neonatal complications and
ing abnormal trophoblast invasion of spiral arteries and a
death.
reduction in vascular resistance in the uteroplacental circu-
• Doppler ultrasonography of the uterine arteries is a promis-
lation.4–6 Although the incidence of pre-eclampsia in the
ing technique for predicting these perinatal complications.
general obstetric population is only 5%, there is a potential
• More research is needed to determine the ideal timing of
for serious adverse outcomes.1,3,7,8 Maternal complications
uterine artery Doppler ultrasonography and the ideal combi-
include the HELLP syndrome (hemolytic anemia, elevated
nation of this technology with other antenatal screening
liver enzymes, low platelet count), eclampsia, coagulopathy,
tests in an effort to improve perinatal outcomes.
stroke and death.1,7,8 Newborns affected by intrauterine
growth restriction are at increased risk for hypertension,
2 cardiovascular disease and diabetes later in life.9 Accurate
procedure has been reported in numerous studies to be a
4
2
0 prediction of pre-eclampsia and intrauterine growth restric-
promising technique for predicting the level of risk for pre-
8
a
j
.
0 tion is therefore paramount to providing appropriate ante-
eclampsia and intrauterine growth restriction.11–15 In a nor-
/
c
m natal surveillance and therapy in an effort to improve peri-
mal pregnancy, impeded flow in the uterine artery decreases
3
0 natal outcomes.
with increasing gestational age.
.
1
5
The uteroplacental circulation can be assessed by means
Uterine artery Doppler ultrasonography may be performed
I
:
1
0
O
D of Doppler ultrasonography of the uterine arteries.10 This
via the transvaginal or transabdominal route in the first or
second trimester. Uterine artery waveforms are reported to be
readily obtainable in more than 95% of patients.15 The uterine
artery is identified with the use of colour Doppler ultrasonog-
raphy (Figure 1). Pulsed-wave Doppler ultrasonography is
then used to obtain waveforms (Figure 2). Various indices can
be calculated and assessed.
In this issue of CMAJ, Cnossen and colleagues16 report the
results of their systematic review and meta-analysis of studies
in which Doppler assessment of the uterine arteries was used
to predict pre-eclampsia and intrauterine growth restriction.
Their review was extensive: they included 74 studies of pre-
eclampsia and 61 of intrauterine growth restriction, with no
language limitations; they evaluated the accuracy of 15
Doppler indices; and they used well-described and robust sta-
tistical methods for their analyses.
One of the most widely studied Doppler indices is the pul-
satility index (calculated as the peak systolic flow minus the
end diastolic flow divided by the mean flow). An increased
pulsatility index has been associated with an increased risk
for pre-eclampsia and intrauterine growth restriction.13–15
The presence of an early diastolic notch in the waveform (Fig-
ure 3) has also been shown in several studies to be associated
Figure 1: Colour Doppler ultrasound scan showing uterine ar-
tery (arrow).
Lynne McLeod is with the Department of Obstetrics and Gynecology, IWK
Health Centre, Halifax, NS
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
CMAJ • March 11, 2008 • 178(6)
727
© 2008 Canadian Medical Association or its licensors

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Commentary
with adverse outcomes. The likelihood ratio, sensitivity and
Although pre-eclampsia and intrauterine growth restric-
specificity for each Doppler index and specific outcome have
tion are not uncommon and may pose serious health risks to
varied among studies, but the predictive relationship for ad-
both mother and fetus, we are still searching for preventive
verse outcomes has been consistently reported.
strategies for these at-risk pregnancies. The first step is to
Cnossen and colleagues found that uterine artery Doppler
identify patients at risk, followed by increased surveillance
ultrasonography more accurately predicted pre-eclampsia than
and therapy. Uterine artery Doppler ultrasonography in isola-
intrauterine growth restriction and that the most powerful
tion, and perhaps in combination with other modalities, may
Doppler index for predicting pre-eclampsia was an increased
by the key to improved perinatal outcomes in these clinical
pulsatility index with notching in the second trimester. For se-
conditions. In addition to uterine artery Doppler ultrasonog-
vere pre-eclampsia, they found that an increased pulsatility in-
raphy, a variety of proteins and hormones have been studied
dex or bilateral notching best predicted the condition. The au-
as potential early biomarkers of pre-eclampsia and intrauter-
thors’ conclusions are in agreement with those from recent
ine growth restriction. Second-trimester maternal serum
studies.17,18 With respect to intrauterine growth restriction,
screening markers for aneuploidy (the presence of an abnor-
Cnossen and colleagues found that an increased pulsatility in-
mal number of chromosomes), β human chorionic go-
dex alone or in combination with notching was most valuable
nadotropin (β-hCG) and α-fetoprotein have been associated
for predicting intrauterine growth restriction in low-risk
with increased risk.19,20 Alterations in first-trimester serum
women, whereas an increased resistance index was the best
levels of the biomarkers placental protein-13 (PP-13) and
predictor of the condition in high-risk women.
pregnancy-associated plasma protein-A (PAPP-A) have also
One of the challenges of conducting a review in this area is
been reported to be predictors of adverse outcomes.14,17,18,20
the variability in definitions of pre-eclampsia and intrauterine
The purpose of the review by Cnossen and colleagues was not
growth restriction, and in the causes. Maternal and perinatal
to address the potential additional benefit of measuring ma-
outcomes are affected by the severity and duration of the con-
ternal biomarkers. However, consideration of a combination
dition as well as by preventive and therapeutic management
of screening tests in a select patient population may be bene-
strategies. These factors undoubtedly affect individual study
ficial to patients and health care resources.
results. In addition, the studies reviewed by Cnossen and col-
The best screening tests have to be accessible, available
leagues were heterogeneous in their timing of Doppler as-
and relatively inexpensive. They must also provide repro-
sessment, severity of disease and outcomes, and inclusion of
ducible results and be acceptable to patients. Uterine artery
other screening modalities.
Doppler ultrasonography fulfills these criteria and is relatively
easy to perform with training and experience. According to
Cnossen and colleagues’ findings, this procedure could be
done in conjunction with routine anatomy ultrasonography at
18–20 weeks’ gestation. However, in some areas the availabil-
ity of uterine artery Doppler ultrasonography may be limited
to specialized obstetrics ultrasound units.
In conclusion, Cnossen and colleagues are to be com-
mended for their thorough systematic review of the current
literature on this important topic and for increasing our
awareness of the potential benefits of uterine artery Doppler
assessment. More research is needed to identify the ideal tim-
ing of screening with this technology and the ideal combina-
Figure 3: Uterine artery Doppler ultrasound scan showing early
diastolic notch (arrow). The presence of diastolic notches is as-
Figure 2: Uterine artery Doppler ultrasound scan showing nor-
sociated with an increased risk of pre-eclampsia and intrauter-
mal waveform.
ine growth restriction.
728
CMAJ • March 11, 2008 • 178(6)

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Commentary
tion of this technology with other predictors of pre-eclampsia
10.
Campbell S, Pearce JMF, Hackett G, et al. Qualitative assessment of uteroplacental
blood flow: Early screening test for high risk pregnancies. Obstet Gynecol 1986;
and intrauterine growth restriction in an effort to improve
68:649-53.
perinatal outcomes. This would include identification of pa-
11.
Martin AM, Bindra R, Curcio P, et al. Screening for pre-eclampsia and fetal growth
restriction by uterine artery Doppler at 11-14 weeks of gestation. Ultrasound Obstet
tient risk factors and antenatal screening — uterine artery
Gynecol 2001;18:583-6.
Doppler ultrasonography and measurement of maternal
12.
Gomez O, Martinez JM, Figueras F, et al. Uterine artery Doppler at 11–14 weeks of
gestation to screen for hypertensive disorders and associated complications in an
serum biomarkers. The ideal combination would allow health
unselected population. Ultrasound Obstet Gynecol 2005;26:490-4.
care providers to screen the appropriate women and target
13.
Albaiges G, Missfelder-Lobos H, Lees C, et al. One-stage screening for pregnancy
complications by color Doppler assessment of the uterine arteries at 23 weeks’
antenatal surveillance and therapeutic interventions at those
gestation. Obstet Gynecol 2000;96:559-64.
who were at risk for pregnancy complications in hopes of im-
14.
Spencer K, Yu CK, Cowans NJ, et al. Prediction of pregnancy complications by first
trimester maternal serum PAPP-A and free beta-hCG and with second trimester
proving outcomes.
uterine artery Doppler. Prenat Diagn 2005;25:949-53.
15.
Papageorghiou AT, Yu CKH, Bindra R, et al. Multicentre screening for pre-eclampsia
and fetal growth restriction by transvaginal uterine artery Doppler at 23 weeks of ges-
Competing interests: None declared.
tation. Ultrasound Obstet Gynecol 2001;18:441-9.
16.
Cnossen JS, Morris RK, ter Riet G, et al. Use of uterine artery Doppler ultrasonog-
raphy to predict pre-eclampsia and intrauterine growth restriction: a systematic re-
view and bivariable meta-analysis. CMAJ 2008;178:701-11.
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lynne.mcleod@iwk.nshealth.ca
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