Вы находитесь на странице: 1из 50

Utero-placental Doppler ultrasound for improving pregnancy

outcome (Review)
Stampalija T, Gyte GML, Alfirevic Z

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2010, Issue 9
http://www.thecochranelibrary.com

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.1. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 1
Any perinatal death after randomisation. . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.2. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 2
Hypertensive disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.3. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 3
Stillbirth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.4. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 4
Neonatal death. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.5. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 5
Any potentially preventable perinatal death after randomisation. . . . . . . . . . . . . . . . .
Analysis 2.7. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 7
Intrauterine growth restriction. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.9. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 9
Neonatal resuscitation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.12. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 12
Apgar score < 7 at 5 min. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.13. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 13
Neonatal admission to SCBU or NICU.
. . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.15. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 15
Iatrogenic preterm birth (< 37 weeks). . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.16. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 16
Caesarean section (both elective and emergency).
. . . . . . . . . . . . . . . . . . . . .
Analysis 2.17. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 17
Elective caesarean section.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.18. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 18
Emergency caesarean section. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.21. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 21
Gestational age at birth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.22. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 22
Infant birthweight. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

1
1
2
2
4
4
7
8
10
11
11
11
16
25
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
47
47
48
48
48
48

[Intervention Review]

Utero-placental Doppler ultrasound for improving pregnancy


outcome
Tamara Stampalija1 , Gillian ML Gyte2 , Zarko Alfirevic3
1 Department

of Obstetrics and Gynaecology, Childrens Hospital V. Buzzi, Milano, Italy. 2 Cochrane Pregnancy and Childbirth
Group, School of Reproductive and Developmental Medicine, Division of Perinatal and Reproductive Medicine, The University of
Liverpool, Liverpool, UK. 3 School of Reproductive and Developmental Medicine, Division of Perinatal and Reproductive Medicine,
The University of Liverpool, Liverpool, UK

Contact address: Tamara Stampalija, Department of Obstetrics and Gynaecology, Childrens Hospital V. Buzzi, Via Castelvetro 32,
Milano, 20154, Italy. stampta@libero.it.
Editorial group: Cochrane Pregnancy and Childbirth Group.
Publication status and date: New, published in Issue 9, 2010.
Review content assessed as up-to-date: 15 July 2010.
Citation: Stampalija T, Gyte GML, Alfirevic Z. Utero-placental Doppler ultrasound for improving pregnancy outcome. Cochrane
Database of Systematic Reviews 2010, Issue 9. Art. No.: CD008363. DOI: 10.1002/14651858.CD008363.pub2.
Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT
Background
Impaired placentation can cause some of the most important obstetrical complications such as pre-eclampsia and intrauterine growth
restriction and has been linked to increased fetal morbidity and mortality. The failure to undergo physiological trophoblastic vascular
changes is reflected by the high impedance to the blood flow at the level of the uterine arteries. Doppler ultrasound study of uteroplacental blood vessels, using waveform indices or notching, may help to identify the at-risk women in the first and second trimester
of pregnancy, such that interventions might be used to reduce maternal and fetal morbidity and/or mortality.
Objectives
To assess the effects on pregnancy outcome, and obstetric practice, of routine utero-placental Doppler ultrasound in first and second
trimester of pregnancy in pregnant women at high and low risk of hypertensive complications.
Search methods
We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (June 2010) and the reference lists of identified studies.
Selection criteria
Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of utero-placental vessel waveforms in
first and second trimester compared with no Doppler ultrasound. We have excluded studies where uterine vessels have been assessed
together with fetal and umbilical vessels.
Data collection and analysis
Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We checked data
entry.
Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)
Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Main results
We found two studies involving 4993 participants. The methodological quality of the trials was good. Both studies included women
at low risk for hypertensive disorders, with Doppler ultrasound of the uterine arteries performed in the second trimester of pregnancy.
In both studies, pathological finding of uterine arteries was followed by low-dose aspirin administration.
We identified no difference in short-term maternal and fetal clinical outcomes.
We identified no randomised studies assessing the utero-placental vessels in the first trimester or in women at high risk for hypertensive
disorders.
Authors conclusions
Present evidence failed to show any benefit to either the baby or the mother when utero-placental Doppler ultrasound was used in
the second trimester of pregnancy in women at low risk for hypertensive disorders. Nevertheless, this evidence cannot be considered
conclusive with only two studies included. There were no randomised studies in the first trimester, or in women at high risk. More
research is needed to investigate whether the use of utero-placental Doppler ultrasound may improve pregnancy outcome.

PLAIN LANGUAGE SUMMARY


Doppler ultrasound of blood vessels in the placenta and uterus of pregnant women as a way of improving outcome for babies
and their mothers
One of the main aims of routine antenatal care is to identify mothers or babies at risk of adverse outcomes. Doppler ultrasound
uses sound waves to detect the movement of blood in blood vessels. It is used in pregnancy to study blood circulation in the baby,
the mothers uterus and the placenta. If abnormal blood circulation is identified, then it is possible that medical interventions might
improve outcomes. We set out to assess the value of using Doppler ultrasound of the mothers uterus or placenta (utero-placental
Doppler ultrasound) as a screening tool. Other reviews have looked at the use of Doppler ultrasound on the babies vessels (fetal and
umbilical Doppler ultrasound). We also choose to look at women with low-risk and high-risk pregnancies, and in their first or second
trimesters. This screening offers a potential for benefit, but also a possibility of unnecessary interventions and adverse effects. The
review of randomised controlled trials of routine Doppler ultrasound of the uterus or placenta identified two studies involving 4993
women. All the women were in the second trimester of pregnancy and at low risk for hypertensive disorders. The studies were of good
quality but small in size. We identified no improvements for the baby or the mother. However, more data would be needed to show
whether maternal Doppler is effective, or not, for improving outcomes. We did not find any studies in the first trimester of pregnancy
or in women at risk of high blood pressure disorders. More research is needed on this important aspect of care.

BACKGROUND

Description of the condition


The blood supply to the uterus is provided mainly by the uterine
arteries and also by the ovarian arteries. Once the arterial vessels
reach myometrium, they divide into arcuate arteries, then into
the radial arteries which ultimately branch into the spiral arteries.
During the first and second trimester of pregnancy, trophoblast
invades the spiral arteries - a process that is fundamental for normal
placentation. The most important change, but not the only one,

is replacement of the muscular and elastic arterial layer by collagen


(Espinoza 2006). As the trophoblastic invasion continues during
the first half of pregnancy, the resistance to the blood flow in the
uterine arteries progressively decreases.
The failure to undergo these physiologic vascular changes has
been associated not just with pre-eclampsia (Brosens 1972; Khong
1991; Sibai 2005; Von Dadelszen 2002) and intrauterine growth
restriction (IUGR) (Bernstein 2000; Fisk 2001; Khong 1991), but
also with other maternal diseases such as diabetes mellitus (Khong
1991), lupus erythematosus (Nayar 1996), antiphospholipid antibody syndrome (Levy 1998) and others (Barker 2004).

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Description of the intervention


Doppler ultrasound velocimetry uses the Doppler principle to
analyse the properties of the blood flow in a vessel of interest. This
physical principle explains the observed change in wave frequency
relative to the speed of a moving object. In case of Doppler ultrasound, the emitted ultrasound frequency will change when ultrasound beam encounters moving blood. The principle can be
applied using different ultrasound modalities such as continuouswave Doppler, pulsed-wave Doppler, colour and power Doppler
wave (Burns 1993; Chen 1996; Owen 2001). While colour and
power Doppler provide visualisation of the blood flow and its direction, pulsed Doppler allows reproducible measurements of the
blood velocities. The measurements obtained will reflect, in any
vessel studied, the cardiac contraction force, density of the blood,
vessel wall elasticity, but more importantly peripheral and downstream resistance (Owen 2001).
Physiological process of the trophoblastic invasion of spiral arteries takes place between six and 24 weeks of gestation in normal
pregnancies. The blood flow from the uterine arteries to the placenta will progressively increase during that time. By studying the
uterine arteries with pulse Doppler ultrasound, it is possible to assess the progressive decrease in resistance to blood flow. The rationale of using the Doppler velocimetry of uterine arteries to assess
the failure of the placentation is related to fact that the lack of
physiological transformation of the spiral arteries will cause high
resistance to blood flow within uterus and subsequently in uterine
arteries.
At least 15 different uterine artery Doppler indices have been used
to quantify the uterine arteries perfusion and predict pre-eclampsia and IUGR (Cnossen 2008). The most commonly used indices
are the pulsatility and resistant index (PI and RI) which showed
the highest predictive value (Cnossen 2008). The qualitative description focuses on the presence or absence of early diastolic notch
that could be either unilateral or bilateral.
The abnormal findings in uterine arteries are usually defined as PI
or RI above the 95 percentile at a given gestational age (Albaiges
2000; Bower 1993) and the presence of notching (a qualitative assessment of flow velocity waveform - Harrington 1996). Numerous studies have linked the high impedance and bilateral notching
in uterine arteries to early onset pre-eclampsia, IUGR and higher
perinatal mortality (Aardema 2001; Albaiges 2000; Bower 1993;
Harrington 1996; Olofsson 1993).
Reported sensitivity and detection rate of the uterine artery
Doppler to predict pre-eclampsia in unselected population range
from 50% to 60%, meaning that only half of the women that
subsequently develop the disease will be correctly identified by the
increased resistance in uterine arteries. On the other hand the reported specificity is around 95%, which means that most women
with normal uterine artery Doppler will not develop pre-eclampsia. The performance of uterine artery Doppler as a screening test
is higher when pre-eclampsia is divided in severe or early onset and
mild or late onset pre-eclampsia. In that case, the sensitivity rises

from 80% to 85% for severe pre-eclampsia, requiring delivery before 34 weeks (Papageorghiou 2001; Yu 2005) and 90% for severe
pre-eclampsia indicating delivery before 32 weeks (Papageorghiou
2001).
More recently, the interest for uterine artery measurements has
moved from the second to the first trimester of pregnancy (13+6
to 11+0 weeks of gestation). The rationale of measuring the uterine artery Doppler in the first trimester is the possibility to intervene with some prophylactic therapy such as antithrombotic
drugs while the trophoblastic invasion is still ongoing. The uterine
artery Doppler has been found to be less predictive when compared
with the second trimester examination. Reported detection rate
for uterine artery Doppler alone in the first trimester ranged from
40% to 67% for early onset pre-eclampsia and 15% to 20% for late
onset pre-eclampsia (Martin 2001; Parra 2005). In the attempt to
improve the performance of the uterine artery as a screening test,
new algorithms that take into account the maternal characteristics,
history and/or biochemical markers have been proposed. In fact,
uterine artery Doppler in the first and second trimester, in combination with several biochemical markers, has been extensively
tested as a predictive test for pre-eclampsia and IUGR, and the first
results are encouraging (Nicolaides 2006; Parra 2005; Plasencia
2007; Spencer 2007; Zhong 2010). Nevertheless, at present the
literature comprises several large uncontrolled cohort studies and
as yet there are no randomised studies in this field, and the costeffectiveness remains to be proven.

How the intervention might work


It is hoped that early detection of abnormal placental vasculature, before maternal and fetal complications develop, would allow preventative interventions and more targeted maternal and
fetal surveillance. Low-dose aspirin is an example of a preventative
intervention that could be targeted to those with abnormal uteroplacental Doppler (Askie 2007).

Why it is important to do this review


Doppler ultrasound has become an integral part of obstetric care
(Alfirevic 2010a) and more clinicians are being trained to use it.
Using a non-invasive and relatively easy screening tool such as
Doppler ultrasound of the uterine arteries to predict pre-eclampsia and IUGR is undoubtedly appealing. Early recognition of preeclampsia and IUGR could improve maternal and perinatal outcome by administration antiplatelet therapy, appropriate antihypertensive therapy, medication for fetal lung maturation and early
delivery. Nevertheless, labelling woman as at risk could cause significant anxiety and increase the number of unnecessary examinations and interventions (blood tests, hospital admission and possibly early delivery).

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Criteria for considering studies for this review

revealed versus Doppler of utero-placental vessels concealed) in


first trimester of pregnancy.
2. Doppler ultrasound of utero-placental vessels versus no
Doppler ultrasound of utero-placental vessels (including
comparisons of Doppler ultrasound of utero-placental vessels
revealed versus Doppler of utero-placental vessels concealed) in
second trimester of pregnancy.
3. Comparison of different forms of Doppler ultrasound of
utero-placental vessels versus other types of Doppler ultrasound
of utero-placental vessels in first trimester of pregnancy.
4. Comparison of different forms of Doppler ultrasound of
utero-placental vessels versus other types of Doppler ultrasound
of utero-placental vessels in second trimester of pregnancy.
5. Comparison of different methods of Doppler ultrasound
measurements of utero-placental vessels in first trimester of
pregnancy.
6. Comparison of different methods of Doppler ultrasound
measurements of utero-placental vessels in second trimester of
pregnancy.

Types of studies

Types of outcome measures

This review will complement two other Cochrane reviews that


focus on the fetal and umbilical Doppler ultrasound in highrisk populations (Alfirevic 2010a), and in low-risk populations
(Alfirevic 2010b).

OBJECTIVES
To assess whether the use of utero-placental Doppler ultrasound
(uterine arteries and placental vessels) improves the outcome of
low- and high-risk pregnancies.

METHODS

All randomised trials and quasi-randomised studies comparing


utero-placental Doppler ultrasound (uterine, arcuate, radial and
spiral arteries) in low- and high-risk pregnancies. We planned to
perform sensitivity analysis by trial quality. We included study
abstracts. We have considered cluster trials, though we found none,
but we did not think cross-over trials would be suitable for this
topic.

Types of participants
Pregnant women, considered to be either low- or high-risk, who
had utero-placental Doppler ultrasound performed at first or second trimester of pregnancy. We planned to include twin pregnancies and to perform subgroup analysis for that population but
there were insufficient data.

Types of interventions
Doppler ultrasound of the utero-placental circulation (uterine,
arcuate, radial and spiral arteries) in pregnancies at low and high
risk. We did not include studies that considered the combination
of utero-placental Doppler and fetal or umbilical Doppler in this
review, but did include them in fetal and umbilical Doppler reviews
(Alfirevic 2010a; Alfirevic 2010b).

Comparisons

1. Doppler ultrasound of utero-placental vessels versus no


Doppler ultrasound of utero-placental vessels (including
comparisons of Doppler ultrasound of utero-placental vessels

Primary outcomes

1. Any perinatal death after randomisation.


2. Hypertensive disorders (pre-eclampsia, eclampsia,
haemolysis elevated liver enzymes and low platelets, chronic
hypertension).
Secondary outcomes

1. Stillbirth (as defined by trialists).


2. Neonatal death (as defined by trialists).
3. Any potentially preventable perinatal death.*
4. Serious neonatal morbidity - composite outcome including
hypoxic Ischaemic encephalopathy, intraventricular
haemorrhage, bronchopulmonary dysplasia, necrotising
enterocolitis.
5. IUGR (as defined by the trialists).
6. Fetal distress (as defined by the study authors).
7. Neonatal resuscitation required (as defined by trialists).
8. Infant requiring intubation/ventilation.
9. Infant respiratory distress syndrome.
10. Apgar score less than seven at five minutes.
11. Neonatal admission to special care or intensive care unit, or
both.
12. Preterm birth (birth before 37 completed weeks of
pregnancy):
i) spontaneous preterm birth;
ii) iatrogenic preterm birth.
13. Caesarean section (elective and emergency).
14. Caesarean section - elective.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

15. Caesarean section - emergency.


16. Serious maternal morbidity and mortality (composite
outcome with death of a woman while pregnant or within 42
days of termination of pregnancy).
17. Mothers admission to special care or intensive care unit, or
both.
18. Gestational age at birth.
19. Infant birthweight.
20. Length of infant hospital stay.
21. Length of maternal hospital stay.
* Perinatal death excluding chromosomal abnormalities, termination of pregnancies, birth before fetal viability (as defined by trialists) and fetal death before use of the intervention.

Data collection and analysis


The methodology for data collection and analysis was based on the
Cochrane Handbook of Systematic Reviews of Interventions (Higgins
2008).

Selection of studies
Two review authors (TS, GG) independently assessed for inclusion
all potential studies we identified as a result of the search strategy.
We resolved any disagreement through discussion or, if required,
we consulted the third author (ZA).

Data extraction and management

Search methods for identification of studies

Electronic searches
We contacted the Trials Search Co-ordinator to search the
Cochrane Pregnancy and Childbirth Groups Trials Register (June
2010).
The Cochrane Pregnancy and Childbirth Groups Trials Register
is maintained by the Trials Search Co-ordinator and contains trials
identified from:
1. quarterly searches of the Cochrane Central Register of
Controlled Trials (CENTRAL);
2. weekly searches of MEDLINE;
3. handsearches of 30 journals and the proceedings of major
conferences;
4. weekly current awareness alerts for a further 44 journals
plus monthly BioMed Central email alerts.
Details of the search strategies for CENTRAL and MEDLINE,
the list of handsearched journals and conference proceedings, and
the list of journals reviewed via the current awareness service can
be found in the Specialized Register section within the editorial information about the Cochrane Pregnancy and Childbirth
Group.
Trials identified through the searching activities described above
are each assigned to a review topic (or topics). The Trials Search
Co-ordinator searches the register for each review using the topic
list rather than keywords.

Searching other resources


We searched the reference lists at the end of papers for further
studies.
We did not apply any language restrictions.

We designed a form to extract data. For eligible studies, two review authors (TS, GG) extracted the data using the agreed form,
with additional help at times (Stephania Livio). We resolved discrepancies through discussion or, if required, we consulted the
third author (ZA). We entered data into Review Manager software
(RevMan 2008) (TS) and checked for accuracy (GG).
When information regarding any of the above was unclear, we
attempted to contact authors of the original reports to provide
further details.

Assessment of risk of bias in included studies


Two review authors (TS, GG) independently assessed risk of bias
for each study using the criteria outlined in the Cochrane Handbook
for Systematic Reviews of Interventions (Higgins 2008). We resolved
any disagreement by discussion or by involving the third author
(ZA).

(1) Sequence generation (checking for possible selection


bias)

We describe for each included study the method used to generate


the allocation sequence in sufficient detail to allow an assessment
of whether it should produce comparable groups.
We assessed the method as:
adequate (any truly random process, e.g. random number
table; computer random-number generator);
inadequate (any non-random process, e.g. odd or even date
of birth; hospital or clinic record number);
unclear.

(2) Allocation concealment (checking for possible selection


bias)

We describe for each included study the method used to conceal


the allocation sequence in sufficient detail and determine whether
intervention allocation could have been foreseen in advance of, or
during recruitment, or changed after assignment.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

We assessed the methods as:


adequate (e.g. telephone or central randomisation;
consecutively numbered sealed opaque envelopes);
inadequate (open random allocation; unsealed or nonopaque envelopes, alternation; date of birth);
unclear.

(3) Blinding (checking for possible performance bias)

We describe for each included study the methods used, if any, to


blind study participants and personnel from knowledge of which
intervention a participant received. We judged studies at low risk
of bias if they were blinded, or if we judged that the lack of blinding
could not have affected the results. We assessed blinding separately
for different outcomes or classes of outcomes.
We assessed the methods as:
adequate, inadequate or unclear for participants;
adequate, inadequate or unclear for personnel;
adequate, inadequate or unclear for outcome assessors.

(4) Incomplete outcome data (checking for possible attrition


bias through withdrawals, dropouts, protocol deviations)

We describe for each included study, and for each outcome or class
of outcomes, the completeness of data including attrition and exclusions from the analysis. We state whether attrition and exclusions were reported, the numbers included in the analysis at each
stage (compared with the total randomised participants), reasons
for attrition or exclusion where reported, and whether missing data
were balanced across groups or were related to outcomes. Where
sufficient information was reported, or was supplied by the trial
authors, we have re-included missing data in the analyses which
we undertook. We assessed methods as:
adequate;
inadequate:
unclear.
We were to discuss whether missing data greater than 20% might
impact on outcomes, acknowledging that with long-term follow
up, complete data are difficult to attain. However, none of the
included studies had greater than 20% missing data.

incompletely and so cannot be used; study fails to include results


of a key outcome that would have been expected to have been
reported);
unclear.

(6) Other sources of bias

We describe for each included study any important concerns we


have about other possible sources of bias.
We assessed whether each study was free of other problems that
could put it at risk of bias:
yes;
no;
unclear.

(7) Overall risk of bias

We made explicit judgements about whether studies were at high


risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). With
reference to (1) to (6) above, we assessed the likely magnitude and
direction of the bias and whether we considered it is likely to impact on the findings. We explored the impact of the level of bias
through undertaking sensitivity analyses - see Sensitivity analysis.
Measures of treatment effect

Dichotomous data

For dichotomous data, we present results as summary risk ratio


with 95% confidence intervals.

Continuous data

For continuous data, we used the mean difference if outcomes are


measured in the same way between trials. We used the standardised
mean difference to combine trials that measure the same outcome,
but used different methods.
Unit of analysis issues

(5) Selective reporting bias

We describe for each included study how we investigated the possibility of selective outcome reporting bias and what we found.
We assessed the methods as:
adequate (where it was clear that all of the studys prespecified outcomes and all expected outcomes of interest to the
review have been reported);
inadequate (where not all the studys pre-specified outcomes
have been reported; one or more reported primary outcomes
were not pre-specified; outcomes of interest were reported

Cluster-randomised trials

We would have included cluster-randomised trials in the analyses


along with individually randomised trials, had we identified any.
We would have make adjustments using the methods described
in the Cochrane Handbook for Systematic Reviews of Interventions
(Higgins 2008) using an estimate of the intracluster correlation coefficient (ICC) derived from the trial (if possible), or from another
source. If ICCs from other sources had been used, we would have
reported this and conducted sensitivity analyses to investigate the

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

effect of variation in the ICC. If we had identified both clusterrandomised trials and individually-randomised trials, we would
have planned to synthesise the relevant information. We would
have considered it reasonable to combine the results from both if
there was little heterogeneity between the study designs and the
interaction between the effect of intervention and the choice of
randomisation unit were considered to be unlikely.
We would also have acknowledged any heterogeneity in the randomisation unit and perform a separate meta-analysis.

Cross-over trials

We considered cross-over designs inappropriate for this research


question.

Dealing with missing data


For included studies, we noted levels of attrition. We would have
explored the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis.
For all outcomes, we carried out analyses, as far as possible, on an
intention-to-treat basis, i.e. we attempted to include all participants randomised to each group in the analyses. The denominator
for each outcome in each trial is the number randomised minus
any participants whose outcomes were known to be missing. We
would have excluded data on outcomes where there was greater
than 20% missing data on short term outcomes had we encountered such data.

Assessment of heterogeneity
We assessed statistical heterogeneity in each meta-analysis using
the T (tau-squared), I and Chi statistics. We regarded heterogeneity as substantial if T was greater than zero and either I was
greater than 30% or there was a low P-value (less than 0.10) in the
Chi test for heterogeneity. Where we found heterogeneity and
random-effects was used, we have reported the average risk ratio,
or average mean difference or average standard mean difference.

Assessment of reporting biases


If there had been 10 or more studies in a meta-analysis we would
have investigated reporting biases (such as publication bias) using
funnel plots. We would have assessed funnel plot asymmetry visually, and use formal tests for funnel plot asymmetry. For continuous outcomes, we would have used the test proposed by Egger
1997, and for dichotomous outcomes we would have used the
tests proposed by Harbord 2006. If asymmetry had been detected
by any of these tests or was suggested by a visual assessment, we
would have performed exploratory analyses to investigate it. We
would seek statistical help if necessary.

Data synthesis
We carried out statistical analysis using the Review Manager software (RevMan 2008). We used fixed-effect meta-analysis for combining data where it was reasonable to assume that studies were
estimating the same underlying treatment effect: i.e. where trials
were examining the same intervention, and the trials populations
and methods were judged sufficiently similar. If there was clinical
heterogeneity sufficient to expect that the underlying treatment effects differ between trials, or if substantial statistical heterogeneity
was detected, we would have used random-effects analysis to produce an overall summary, if this was considered clinically meaningful. If an average treatment effect across trials was not clinically
meaningful, we would not have combined heterogeneous trials. If
we used random-effects analyses, the results have been presented
as the average treatment effect and its 95% confidence interval,
the 95% prediction interval for the underlying treatment effect,
and the estimates of T and I (Higgins 2009).
Subgroup analysis and investigation of heterogeneity
We had planned to carry out the following subgroup analyses on
all outcomes:
1. measurements in high-risk population, low-risk population
and unselected population;
2. in singleton and twin pregnancies.
However, there were insufficient data to perform any subgroup
analyses. We had also planned to pull together the three subgroups
for the overall estimation.
For fixed-effect meta-analyses, we had planned to conduct the
planned subgroup analyses classifying whole trials by interaction
tests as described by Deeks 2001. For random-effects meta-analyses, we would have assessed differences between subgroups by inspection of the subgroups confidence intervals; non-overlapping
confidence intervals indicate a statistically significant difference in
treatment effect between the subgroups.
Sensitivity analysis
We would have performed sensitivity analysis on the primary outcomes based on trial quality, separating high-quality trials from
trials of lower quality. High quality would, for the purposes of
this sensitivity analysis, have been defined as a trial having adequate sequence generation and allocation concealment.

RESULTS

Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies; Characteristics of studies awaiting classification.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Results of the search


The search was designed to identify all randomised controlled trials
on assessing the effectiveness of Doppler ultrasound, whether using fetal-umbilical or utero-placental (maternal) vessels. We identified 58 publications from 34 studies, of which we have included
two in this review, involving data on 4993 women and 5009
neonates (Goffinet 2001; Subtil 2003).
We have excluded 30 studies, mainly because they assessed both fetal and umbilical vessels. For further details of trial characteristics,
please refer to the tables of Characteristics of included studies and
Characteristics of excluded studies. Two studies are awaiting classification as we are trying to locate the authors but they both appear
to remain unpublished (Ellwood 1997; Snaith 2006). The large
number of excluded studies reflects the fact that the search was
designed for all Doppler ultrasound studies, including both uteroplacental vessels and fetal-umbilical vessels. Most of the studies
identified focused on fetal-umbilical vessels and are included by
two other Doppler ultrasound reviews (Alfirevic 2010a; Alfirevic
2010b).

Included studies compared uterine artery Doppler assessments in


the experimental group with no uterine artery Doppler performed
in the control groups (Goffinet 2001; Subtil 2003). In both studies, low-dose aspirin was administrated in cases of abnormal uterine artery Doppler findings (Goffinet 2001; Subtil 2003).
Both studies were of assessments of women in the second trimester,
around time for fetal anomaly scan, and both included women at
low risk for hypertensive disorders (Goffinet 2001; Subtil 2003).
One of the studies involved a mixture of singleton and twin pregnancies (Subtil 2003), while the other did not state specifically if
it included multiple pregnancies, although reported numbers suggest only singleton pregnancies were included (Goffinet 2001).
Excluded studies
We excluded 30 studies, mostly because they assessed umbilical
artery Doppler ultrasound. See Characteristics of excluded studies.

Risk of bias in included studies


Included studies

The quality of the three included studies was reasonable, although


blinding was not possible (Figure 1).

Figure 1. Methodological quality summary: review authors judgements about each methodological quality
item for each included study.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Allocation
Both studies had adequate sequence generation and concealment
allocation (Goffinet 2001; Subtil 2003).
Blinding
Blinding women and/or staff in these trials was not generally feasible. Some outcomes like induction of labour and caesarean section may be influenced by the knowledge of Doppler results, but
it may be possible to avoid bias in neonatal assessment. Unfortunately, the information on the attempts to protect against biased
assessment was not available.
Incomplete outcome data
The two studies had adequate outcome data (Goffinet 2001; Subtil
2003). One of the studies awaiting classification (Ellwood 1997)
aimed to recruit 524 women, but undertook the analysis after 364
women had entered the trial, though data were available on only
164. As this was not a block randomisation, we cannot be sure
these are randomised groups being compared so we are awaiting
the full study to be reported before including any data.

We found no studies assessing uterine artery Doppler ultrasound


in the first trimester.

2. Uterine artery Doppler ultrasound versus no


Doppler ultrasound, 2nd trimester (two studies, 4993
women)
We identified two studies assessing uterine artery Doppler ultrasound in the second trimester in women at low risk for hypertensive disorders (Goffinet 2001; Subtil 2003). Both were full publications (Goffinet 2001; Subtil 2003). Overall the quality of the
included studies was good for the main criteria of randomisation, allocation concealment and low percentage of missing data
(Goffinet 2001; Subtil 2003), see Figure 1.

Primary outcomes

It is important to emphasise that this review remains underpowered to detect clinically important differences in serious maternal
and neonatal morbidity.

Selective reporting
We assessed both included studies as unclear because we did not
assess the trial protocols.
Other potential sources of bias
One study appeared free of other biases (Subtil 2003), whilst for
the other this was unclear (Goffinet 2001).

Sensitivity analyses

For sensitivity analyses by quality of studies, we have used both adequate labelled sequence generation and adequate allocation concealment as essential criteria for high quality. Two of three studies met these criteria (Goffinet 2001; Subtil 2003), see Figure 1.
However, we feel there are insufficient data to perform a sensitivity
analysis by quality.

Effects of interventions

1. Uterine artery Doppler ultrasound versus no


Doppler ultrasound, 1st trimester (no studies)

Any perinatal death after randomisation


The difference in perinatal mortality between two groups was not
statistically significant (average risk ratio (RR) 1.61, 95% confidence interval (CI) 0.48 to 5.39, two studies, 5009 babies, Analysis
2.1). The heterogeneity was high (T = 0.55, Chi P = 0.06, I
= 72%) and therefore, we used the random-effects model for the
analysis. We were unable to calculate the prediction interval as
there were only two studies.
Subtil 2003 reported significantly fewer deaths in the control
group (RR 3.14, 95% CI 1.10 to 8.98). This difference was contributed to by 17 abortions or medically indicated terminations of
pregnancy in the 1253 women in the Doppler group (1.4%) compared with three out of 617 in the control group (0.5%). In addition, 78 of the 1253 women randomised to Doppler group (6.2%)
did not receive their allocated treatment. The reason was termination of pregnancies for medical or social reasons in 15 women and
perinatal deaths in two babies, but the reasons for the remainder
of the women not receiving the Doppler ultrasound were not documented. The analysis for Any potentially preventable perinatal
death after randomisation which excluded all terminations and
perinatal deaths for chromosomal abnormalities is more clinically
relevant and showed no detectable difference (see below).

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Hypertensive disorders

Sensitivity analysis

There was no difference identified in maternal hypertensive disorders between two groups (RR 1.08, 95% CI 0.87 to 1.33, two
studies, 4987 women, Analysis 2.2).

Since we assessed both studies as adequate for sequence generation


and allocation concealment (Goffinet 2001; Subtil 2003), we did
not undertake sensitivity analysis by quality.

Secondary outcomes

DISCUSSION

We found no significant difference in the pooled estimate of the intervention effect for the range of secondary outcomes with low heterogeneity where a fixed-effect meta-analysis was used. Most prespecified secondary outcomes had high heterogeneity and therefore an intervention effect estimate across studies was calculated
using random-effects.
There was no significant difference in stillbirths (average RR 1.44,
95% CI 0.38 to 5.49, two studies, 5003 babies, random-effects
T = 0.70, Chi P = 0.04, I = 75%, Analysis 2.3), or for neonatal
deaths (RR 2.39, 95% CI 0.39 to 14.83, two studies, 5009 babies,
Analysis 2.4). Similarly for Any potentially preventable perinatal
death after randomisation (average RR 1.29, 95% CI 0.21 to 7.94,
two studies, 5009 babies, random-effects T 1.09, Chi P = 0.11, I
= 60%, Analysis 2.5). These data should be interpreted cautiously
because the numbers are small and heterogeneity is high.
The data for neonatal admission to special care baby unit (SCBU)
or neonatal intensive care unit (NICU) (RR 1.12, 95% CI 0.92
to 1.37, two studies, 5001 babies, Analysis 2.13) and iatrogenic
preterm birth (average RR 0.92, 95% CI 0.51 to 1.65, two studies,
4982 women, random-effects T = 0.09, Chi P = 0.15, I = 51%,
Analysis 2.15) are consistent with the overall picture showing no
significant difference in two groups. The meta-analysis also failed
to identify any difference in IUGR (average RR 0.98, 95% CI
0.64 to 1.50, two studies, 5006 babies, random-effects T = 0.08,
Chi P = 0.02, I = 82%, Analysis 2.7), although there was high
heterogeneity, so it is also possible that there are different effects
in the different studies, for unknown reasons.
Only one study assessed neonatal resuscitation (RR 0.94, 95% CI
0.75 to 1.19, 3133 babies, Analysis 2.9), Apgar score less than
seven at five minutes (RR 1.08, 95% CI 0.48 to 2.45, 3133 babies)
(Analysis 2.12) and caesarean sections (emergency plus elective)
(RR 1.09, 95% CI 0.91 to 1.29, 3133 women) (Analysis 2.16).
We found no significant difference for any of these outcomes.
None of the studies assessed the following outcomes: Serious
neonatal morbidity, Fetal distress, Infant requiring intubation/
ventilation, Infant respiratory distress syndrome, Spontaneous
preterm birth, Serious maternal morbidity and Maternal admission to special care.

Increasing interest in maternal Doppler in first and second


trimester led us to undertake this review which completes a trio
of reviews on Doppler ultrasound in pregnancy. The other two
reviews focused on the use of fetal-umbilical Doppler ultrasound
in high risk (Alfirevic 2010a) and normal pregnancies (Alfirevic
2010a).

Non-prespecified outcomes

We did not include any non-prespecified outcomes.

Despite wide use of uterine artery Doppler ultrasound in clinical


practice, we identified just two randomised studies assessing this
intervention in the second trimester of pregnancy involving 4993
women at low risk of hypertensive disorders (Goffinet 2001; Subtil
2003) and found no difference in any perinatal or maternal outcomes. Considering that both included studies involved women at
low risk for hypertensive disorders, this could possibly explain the
lack of benefit identified for uterine artery Doppler application
as incidence of adverse outcomes was low (any potentially preventable perinatal death 0.4%, hypertensive disorders 7%, IUGR
11%).
In both studies (Goffinet 2001; Subtil 2003), the finding of pathological uterine artery Doppler was followed by low-dose aspirin
administration. When interpreting these data, it is important to
highlight the presence of heterogeneity and small number of participants that makes our review underpowered rare events such as
perinatal mortality and severe maternal outcomes.
Suprisingly, lower perinatal mortality was observed in the control group in one study (Subtil 2003: risk ratio 3.14, 95% confidence interval 1.10 to 8.98, Analysis 2.1). This could be possibly
explained by a higher percentage of women with termination of
pregnancy or perinatal death that occurred in the Doppler group
by chance before the Doppler ultrasound was carried out.

Summary of main results


We found no differences in any of the perinatal and maternal
outcomes when comparing uterine artery Doppler ultrasound in
the second trimester in women at low risk for hypertensive disorders versus controls. There were no studies of women in the first
trimester.

Overall completeness and applicability of


evidence

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

There were only two studies involving 4993 women, and clearly
the meta-analysis remains underpowered to show clinically important differences in primary outcomes. The identification of an
abnormal results also needs an effective intervention before the
screening test can be said to be helpful.

Quality of the evidence


The studies were of reasonable quality, but involved insufficient
numbers of women overall to assess the rare outcomes of perinatal
death and morbidity.

Potential biases in the review process


We attempted to minimise bias in a number of ways; two review
authors assessed eligibility for inclusion, carried out data extraction
and assessed risk of bias. Each worked independently. Nevertheless,
the process of assessing risk of bias, for example, is not an exact
science and includes many personal judgements.

Agreements and disagreements with other


studies or reviews
Findings from this meta-analysis are not in disagreement with
other non-randomised studies that examined the role of uterine
arteries in low-risk population in second trimester of pregnancy.

AUTHORS CONCLUSIONS

Implications for practice


Data in this meta-analysis failed to show that the use of uterine
artery Doppler in second trimester in low-risk population for hypertensive disorders provides benefit for the baby or mother.
Uterine artery Doppler ultrasound is widely used in high-risk pregnancy and progressively its use is spreading into the first trimester,
although there are no randomised studies to show clear benefit in
this population of women. Futher research is needed to prove the
appropriateness of this clinical practice application.

Implications for research


As previously highlighted, larger studies are needed with enough
power to show clearly the presence or absence of benefit when
using uterine artery Doppler ultrasound in second trimester in
low-risk women for hypertensive disorders. Moreover, randomised
controlled trials of uterine artery Doppler in the first and second
trimester, in combination with womans history and/or biochemical serum markers, are needed to evaluate the benefit of combined
models.

ACKNOWLEDGEMENTS
We would also like to thank Stefania Livio, who helped with some
of the data extractions, and Eugenie Ong, who translated the de
Rochambeau 1992 study.
As part of the pre-publication editorial process, this review has been
commented on by two peers (an editor and referee who is external
to the editorial team), a member of the Pregnancy and Childbirth
Groups international panel of consumers and the Groups Statistical Adviser.

REFERENCES

References to studies included in this review


Goffinet 2001 {published data only}
Goffinet F, Aboulker D, Paris-Llado J, Bucourt M, Uzan
M, Papiernik E, et al.Screening with a uterine doppler in
low risk pregnant women followed by low dose aspirin in
women with abnormal results: a multicenter randomised
controlled trial. British Journal of Obstetrics and Gynaecology
2001;108:5108.
Subtil 2003 {published data only}

Subtil D, Goeusse P, Houfflin-Debarge V, Puech F,


Lequien P, Breart G, et al.Randomised comparison of
uterine artery doppler and aspirin (100 mg) with placebo
in nulliparous women: the Essai Regional Aspirine MereEnfant study (part 2). BJOG: an International Journal of

Obstetrics & Gynaecology 2003;110(5):48591.


Subtil D, Truffert P, Goeusse P, Dufour P, Uzan S, Breart
G, et al.Value of systematic doppler +/- low dose aspirin
to prevent vascular complications in primigravidae.
Hypertension in Pregnancy 2000;19(Suppl 1):9.

References to studies excluded from this review


Almstrom 1992 {published data only}

Almstrom H, Axelsson O, Cnattingius S, Ekman G,


Maesel A, Ulmsten U, et al.Comparison of umbilical-artery
velocimetry and cardiotocography for surveillance of smallfor-gestational-age fetuses. Lancet 1992;340:93640.
Almstrom H, Axelsson O, Ekman G, Ingemarsson I,
Maesel A, Arstrom K, et al.Umbilical artery velocimetry
may influence clinical interpretation of intrapartum

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

11

cardiotocograms. Acta Obstetricia et Gynecologica


Scandinavica 1995;74:5269.
Marsal K, Almstrom H, Axelsson O, Cnattingius S, Ekman
G, Maesel A, et al.Umbilical artery velocimetry is more
effective than cardiotocography for surveillance of growth
retarded fetuses. Journal of Perinatal Medicine 1991;19
(Suppl 2):84.
Ben-Ami 1995 {published data only}
Ben-Ami M, Battino S, Geslevich Y, Shalev E. A random
single Doppler study of the umbilical artery in the evaluation
of pregnancies complicated by diabetes. American Journal of
Perinatology 1995;12(6):4378.
Biljan 1992 {published data only}

Biljan M, Haddad N, McVey K, Williams J. Efficiency of


continuous-wave Doppler in screening high risk pregnancies
in a district general hospital (a prospective randomized
study on 674 singleton pregnancies). Proceedings of 26th
British Congress of Obstetrics and Gynaecology; 1992 July
7-10; Manchester, UK. 1992:6.
Biljan MM, McVey KP, Haddad NG. The value of
continuous wave doppler assessment of fetal umbilical artery
in management of at risk pregnancies. Proceedings of 2nd
European Congress on Prostaglandins in Reproduction;
1991 April 30-May 3; The Hague, Netherlands. 1991:189.
Burke 1992 {published data only}

Burke G, Stuart B, Crowley P, Ni Scanaill S, Drumm J.


Does Doppler ultrasound alter the management of high-risk
pregnancy?. Care concern and cure in perinatal medicine.
13th European Congress of Perinatal Medicine; 1992 May;
Amsterdam, The Netherlands. Parthenon, 1992:597604.
Burke G, Stuart B, Crowley P, Ni Scanaill S, Drumm J.
Does Doppler ultrasound alter the management of high-risk
pregnancy?. Journal of Perinatal Medicine 1992;20(Suppl
1):266.
Davies 1992 {published data only}
Breart G, Uzan S, Uzan M. Doppler ultrasound screening
during pregnancy [Letter; comment]. Lancet 1993;341
(8843):5012.
Davies J, Spencer J, Gallivan S. Randomised trial of Doppler
screening in a general obstetric population. Proceedings of
26th British Congress of Obstetrics and Gynaecology; 1992
July 7-10; Manchester, UK. 1992:316.

Davies JA, Gallivan S, Spencer JAD. Randomised


controlled trial of doppler ultrasound screening of placental
perfusion during pregnancy. Lancet 1992;340:1299303.
Spencer JAD, Davies JA, Gallivan S. Randomised trial of
routine Doppler screening during pregnancy. Journal of
Maternal Fetal Investigation 1992;1:126.
de Rochambeau 1992 {published data only}
de Rochambeau B, Jabbour N, Mellier G. Umbilical doppler
velocimetry in prolonged pregnancies [La velocimetrie
Doppler ombilicale dans les grossesses prolongees.]. Revue
Francaise de Gynecologie et d Obstetrique 1992;87(5):
28994.

Doppler 1997 {published data only}


Doppler French Study Group. A randomised controlled
trial of Doppler ultrasound velocimetry of the umbilical
artery in low risk pregnancies Doppler French Study Group.
British Journal of Obstetrics and Gynaecology 1997;104(4):
41924.
Giles 2003 {published data only}
Giles W, Bisits A, OCallaghan S. The doppler assessment
in multiple pregnancy study (damp) and metaanalyses
of doppler and twins. American Journal of Obstetrics and
Gynecology 2000;182(1 Pt 2):S17.

Giles W, Bisits A, OCallaghan S, Gill A. The doppler


assessment in multiple pregnancy randomised controlled
trial of ultrasound biometry versus umbilical artery doppler
ultrasound and biometry in twin pregnancy. BJOG: an
international journal of obstetrics and gynaecology 2003;110
(6):5937.
Gonsoulin 1991 {published data only}
Gonsoulin W. Umbilical artery Doppler waveform analysis:
a randomized study on effect on outcome. American Journal
of Obstetrics and Gynecology 1991;164:370.
Haley 1997 {published data only}
Haley J, Tuffnell DJ, Johnson N. Randomised controlled
trial of cardiotocography versus umbilical artery Doppler in
the management of small for gestational age fetuses. British
Journal of Obstetrics and Gynaecology 1997;104(4):4315.
Hofmeyr 1991 {published data only}
Hofmeyr GJ, Pattinson R, Buckley D, Jennings J, Redman
CWG. Umbilical artery resistance index as a screening
test for fetal well-being. II. Randomized feasibility study.
Obstetrics & Gynecology 1991;78:35962.
Johnstone 1993 {published data only}
Johnstone FD, Prescott R, Hoskins P, Greer IA, McGlew
T, Compton M. The effect of introduction of umbilical
Doppler recordings to obstetric practice. British Journal of
Obstetrics and Gynaecology 1993;100:73341.
Mason 1993 {published data only}
Mason GC, Lilford RJ, Porter J, Nelson E, Tyrell S.
Randomised comparison of routine vs highly selective use of
Doppler ultrasound in low risk pregnancies. British Journal
of Obstetrics and Gynaecology 1993;100:1303.
McCowan 1996 {published data only}
McCowan LME, Harding J, Roberts AB, Barker S,
Townend K. Perinatal morbidity in small for gestational age
fetuses in relation to umbilical doppler. Proceedings of the
14th Annual Congress of the Australian Perinatal Society in
conjunction with the New Zealand Perinatal Society; 1996
March 24-27; Adelaide, Australia. 1996:P10.
McParland 1988 {published data only}
McParland P, Pearce JM. Doppler blood flow in pregnancy.
Placenta 1988;9:42750.
Neales 1994 {published data only}
Neales K. A randomised controlled study to assess the use
of Doppler ultrasound in the management of patients with
intrauterine growth retardation. Personal communication
1994.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

12

Newnham 1991 {published data only}


Newnham JP, ODea MRA, Reid KP, Diepeveen DA.
Doppler flow velocity waveform analysis in high risk
pregnancies: a randomized controlled trial. British Journal
of Obstetrics and Gynaecology 1991;98:95663.
Newnham 1993 {published data only}
Evans S, Newnham J, MacDonald W, Hall C.
Characterisation of the possible effect on birthweight
following frequent prenatal ultrasound examinations. Early
Human Development 1996;45(3):20314.
Newnham J, Macdonald W, Gurrin L, Evans S, Landau L,
Stanley F. The effect of frequent prenatal ultrasound on
birthweight: follow-up at one year of age. Proceedings
of the 14th Annual Congress of the Australian Perinatal
Society in conjunction with the New Zealand Perinatal
Society; 1996 March 24-27; Adelaide, Australia. 1996:A26.
Newnham JP, Doherty DA, Kendall GE, Zubrick SR,
Landau LL, Stanley FJ. Effects of repeated prenatal
ultrasound examinations on childhood outcome up to 8
years of age: follow-up of a randomised controlled trial.
Lancet 2004;364:203844.

Newnham JP, Evans SF, Michael CA, Stanley FJ, Landau


LI. Effects of frequent ultrasound during pregnancy: a
randomised controlled trial. Lancet 1993;342:88791.
Nienhuis 1997 {published data only}
Nienhuis SJ. Costs and effects of Doppler ultrasound
measurements in suspected intrauterine growth retardation.
A randomised clinical trial. Thesis. Maastricht: Universitaire
Pers Maastricht, 1995.
Nienhuis SJ, Ruissen CJ, Hoogland HJ, Gerver JW, Vles
J, de Haan J. Cost-effectiveness of a doppler policy in
suspected intrauterine growth retardation - a randomized
controlled trial. International Journal of Gynecology and
Obstetrics 1991;36 Suppl:32.

Nienhuis SJ, Vles JS, Gerver WJ, Hoogland HJ.


Doppler ultrasonography in suspected intrauterine growth
retardation: a randomized clinical trial. Ultrasound in
Obstetrics & Gynecology 1997;9(1):613.
Ruissen CJ, Nienhuis SJ, Hoogland HJ, Vles JFH, Gerver
WJ, De Haan J. Cost-effectiveness of a Doppler based policy
of suspected intrauterine growth retardation - a randomised
controlled trial. Journal of Maternal Fetal Investigation 1992;
1:126.
Nimrod 1992 {published data only}
Nimrod C, Yee J, Hopkins C, Pierce P, Lange I, Fick G, et
al.The utility of pulsed Doppler studies in the evaluation of
postdate pregnancies. Journal of Maternal Fetal Investigation
1992;1:127.
Norman 1992 {published data only}
Norman K, Pattinson RC, Carstens E. Doppler velocimetry
in recurrent pregnancy loss: is there a role?. Proceedings of
11th Conference on Priorities in Perinatal Care in South
Africa; 1992 March; Caledon, South Africa. 1992:714.
Omtzigt 1994 {published data only}
Omtzigt AWJ. Clinical value of umbilical doppler velocimetry.
Utrecht: University of Utrecht, 1990.
Omtzigt AWJ, Bruinse HW, Reuwer PJHM. A randomized

controlled trial on the clinical value of umbilical Doppler


velocimetry: neonatal outcome. Proceedings of 12th
European Congress of Perinatal Medicine; 1990 Sept 1114; Lyon, France. 1990:189.
Omtzigt AWJ, Bruinse HW, Reuwer PJHM. A randomized
controlled trial on the clinical value of umbilical Doppler
velocimetry. I. Obstetrical management. Proceedings of
12th European Congress of Perinatal Medicine; 1990 Sept
11-14; Lyon, France. 1990:210.

Omtzigt AWJ, Reuwer PJHM, Bruinse HW. A randomized


controlled trial on the clinical value of umbilical Doppler
velocimetry in antenatal care. American Journal of Obstetrics
and Gynecology 1994;170:62534.
Pattinson 1994 {published data only}
Pattinson R, Norman K, Odendaal HJ. Management of
fetuses suspected of IUGR but with EDVs of the umbilical
artery: a randomised controlled trial. Proceedings of 26th
British Congress of Obstetrics and Gynaecology; 1992 July
7-10; Manchester, UK. 1992:5.

Pattinson RC, Norman K, Odendaal HJ. The role of


Doppler velocimetry in the management of high risk
pregnancies. British Journal of Obstetrics and Gynaecology
1994;101:11420.
Pattinson RC, Norman K, Odendaal HJ. The role of
doppler velocimetry in the management of pregnancies:
a randomized controlled trial. Proceedings of 11th
Conference on Priorities in Perinatal Care in South Africa;
1992 March; Caledon, South Africa. 1992:5963.
Pearce 1992 {published data only}
Pearce JM. The application of uteroplacental waveforms to
complicated pregnancies. In: Pearce JMP editor(s). Doppler
ultrasound in perinatal medicine. Oxford: Oxford University
Press, 1992:15977.
Schneider 1992 {published data only}
Schneider KT, Amberg-Wendland D, Renz S, Furstenau
U. Prospective randomized study of the clinical value
of Doppler sonography as a screening procedure
[Prospektiv randomisierte Untersuchung zum klinischen
Wert der Dopplersonographie als Screeningverfahren].
Gynakologische Rundschau 1991;31(Suppl 1):13940.
Schneider KTM, Renz S, Furstenau U, Amberg-Wendland
D, Prochaska D, Graeff H. Doppler flow measurements as a
screening method during pregnancy: is it worth the effort?.
Journal of Maternal Fetal Investigation 1992;1:125.
Scholler 1993 {published data only}
Scholler J, Putz M, Sainz HG, Altrichter R, Philipp
K. Value of Doppler sonography in management of
non-risk pregnancies at term [Der Stellenwert der
Dopplersonographie bei der Betreuung von Nicht
Risikoschwangerschaften am Geburtstermin]. Gynakologisch
Geburtshilfliche Rundschau 1993;33(1 Suppl):1189.
Trudinger 1987 {published data only}
Trudinger BJ, Cook CM, Giles WB, Connelly AJ,
Thompson RS. Umbilical artery flow velocity waveforms in
high-risk pregnancy: randomised controlled trial. Lancet
1987;1:18890.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

13

Tyrrell 1990 {published data only}


Lilford RJ. Fetal assessment in laboratory vs standard
management of high risk pregnancy. Personal
communication 1989.

Tyrrell SN, Lilford RJ, MacDonald HN, Nelson EJ,


Porter J, Gupta JK. Randomized comparison of routine vs
highly selective use of Doppler ultrasound and biophysical
scoring to investigate high risk pregnancies. British Journal
of Obstetrics and Gynaecology 1990;97:90916.
Whittle 1994 {published data only}
Hanretty KP. Randomized study of doppler waveforms in
umbilical and uterine arteries as a screening method to
identify the compromised fetus. Personal communication
1988.
Whittle MJ, Hanretty KP, Primrose MH, Neilson JP.
Screening for the compromised fetus: a randomized trial
of umbilical artery velocimetry in unselected pregnancies.
American Journal of Obstetrics and Gynecology 1994;170:
5559.
Williams 2003 {published data only}
Williams K, Farquharson D, Bebbington M, Dansereau J,
Galerneau F, Wilson RD, et al.A randomized controlled
clinical trial comparing non stress testing versus doppler
velocimetry as a screening test in a high risk population
[abstract]. American Journal of Obstetrics and Gynecology
2000;182(1 Pt 2):S109.

Williams KP, Farquharson DF, Bebbington M, Dansereau


J, Galerneau F, Wilson RD, et al.Screening for fetal wellbeing in a high-risk pregnant population comparing the
nonstress test with umbilical artery doppler velocimetry: a
randomized controlled clinical trial. American Journal of
Obstetrics and Gynecology 2003;188(5):136671.

References to studies awaiting assessment


Ellwood 1997 {published data only}
Ellwood D. Predicting adverse pregnancy outcomes with
ultrasound. Personal communication 1997.
Snaith 2006 {published data only}
Snaith V. Support and reassurance in antenatal care (ongoing
trial). Current Controlled Trials (http://controlledtrials.com/mrct) (accessed 21 March 2006).

Additional references
Aardema 2001
Aardema MW, Oosterhof H, Timmer A, van Rooy
I, Aarnoudse JG. Uterine artery Doppler flow and
uteroplacental vascular pathology in normal pregnancies
and pregnancies complicated by pre-eclampsia and small for
gestational age fetuses. Placenta 2001;22(5):40511.
Albaiges 2000
Albaiges G, Missfelder-Lobos H, Lees C, Parra M,
Nicolaides KH. One-stage screening for pregnancy
complications by color Doppler assessment of the uterine
arteries at 23 weeks gestation. Obstetrics & Gynecology
2000;96(4):55964.

Alfirevic 2010a
Alfirevic Z, Stampalija T, Gyte GML, Neilson JP. Fetal and
umbilical Doppler ultrasound in high risk pregnancies.
Cochrane Database of Systematic Reviews 2010, Issue 1.
[DOI: 10.1002/14651858.CD007529.pub2]
Alfirevic 2010b
Alfirevic Z, Stampalija T, Gyte GML. Fetal and umbilical
Doppler ultrasound in normal pregnancy. Cochrane
Database of Systematic Reviews 2010, Issue 8. [DOI:
10.1002/14651858.CD001450.pub3]
Askie 2007
Askie LM, Duley L, Henderson-Smart DJ, Stewart LA.
Antiplatelet agents for prevention of pre-eclampsia: a metaanalysis of individual patient data. Lancet 2007;369:
17918.
Barker 2004
Barker DJ. The developmental origins of chronic adult
disease. Acta Paediatrica. Supplement 2004;93(446):2633.
Bernstein 2000
Bernstein IM, Horbar JD, Badger GJ, Ohlsson A, Golan
A. Morbidity and mortality among very-low-birth neonates
with intrauterine growth restriction. The Vermont Oxford
Network. American Journal of Obstetrics and Gynecology
2000;182:198206.
BJOG 1995
Anonymous. Retraction of articles. British Journal of
Obstetrics and Gynaecology 1995;102(11):853.
Bower 1993
Bower S, Schuchter K, Campbell S. Doppler ultrasound
screening as part of routine antenatal screening: prediction
of pre-eclampsia and intrauterine growth retardation.
British Journal of Obstetrics and Gynaecology 1993;100(11):
98994.
Brosens 1972
Brosens IA, Robertson WB, Dixon HG. The role of the
spiral arteries in the pathogenesis of preeclampsia. Obstetrics
and Gynecology Annual 1972;1:17791.
Burns 1993
Burns PN. Principles of Doppler and colour flow. Radiology
in Medicine 1993;85:316.
Chen 1996
Chen JF, Fowlkes JB, Carson PL, Rubin JM, Adler RS.
Autocorrelation of integrated power Doppler signals and its
application. Ultrasound in Medicine and Biology 1996;22:
10537.
Cnossen 2008
Cnossen JS, Morris RK, ter Riet G, Mol BW, van der Post
JA, Coomarasamy A, et al.Use of uterine artery Doppler
ultrasonography to predict pre-eclampsia and intrauterine
growth restriction: a systematic review and bivariable metaanalysis. Canadian Medical Association Journal 2008;178
(6):70111.
Deeks 2001
Deeks JJ, Altman DG, Bradburn MJ. Statistical methods
for examining heterogeneity and combining results from

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

14

several studies in meta-analysis. In: Egger M, Davey Smith


G, Altman DG editor(s). Systematic reviews in health care:
meta-analysis in context. London: BMJ Books, 2001.
Egger 1997
Egger M, Smith GD, Schneider M, Minder C. Bias in
meta-analysis detected by a simple, graphical test. BMJ
1997;315:62934.
Espinoza 2006
Espinoza J, Romero R, Kim YM, Kusanovic JP, Hassan
S, Erez O, et al.Normal and abnormal transformation of
the spiral arteries during pregnancy. Journal of Perinatal
Medicine 2006;34:44758.
Fisk 2001
Fisk NM, Smith RP. Fetal growth restriction; small for
gestational age. In: Chamberlain G, Steer P editor(s).
Turnbulls obstetrics. 3rd Edition. Edinburgh: Churchill
Livingstone, 2001:197209.
Harbord 2006
Harbord RM, Egger M, Sterne JA. A modified test for
small-study effects in meta-analyses of controlled trials
with binary endpoints. Statistics in Medicine 2006;25(20):
344357.
Harrington 1996
Harrington K, Cooper D, Lees C, Hecher K, Campbell S.
Doppler ultrasound of the uterine arteries: the importance
of bilateral notching in the prediction of pre-eclampsia,
placental abruption or delivery of small-for-gestational-age
baby. Ultrasound in Obstetrics and Gynecology 1996;7(3):
1828.
Higgins 2008
Higgins JPT, Green S, editors. Cochrane Handbook for
Systematic Reviews of Interventions Version 5.0.1 [updated
September 2008]. The Cochrane Collaboration, 2008.
Available from www.cochrane-handbook.org.
Higgins 2009
Higgins JP, Thompson SG, Spiegelhalter DJ. A reevaluation of random-effects meta-analysis. Journal of the
Royal Statistical Society, Series A, (Statistics in Society) 2009;
172(1):13759.
Khong 1991
Khong TY. Acute atherosis in pregnancies complicated by
hypertension, small-for-gestational-age infants, and diabetes
mellitus. Archives of Pathology and Laboratory Medicine
1991;115(7):7225.
Levy 1998
Levy RA, Avvad E, Oliviera J, Porto LC. Placental pathology
in antiphospholipid syndrome. Lupus 1998;7(Suppl 2):S81.
Martin 2001
Martin AM, Bindra R, Curcio P, Cicero S, Nicolaides KH.
Screening for pre-eclampsia and fetal growth restriction
by uterine artery Doppler at 11-14 weeks of gestation.
Ultrasound in Obstetrics and Gynecology 2001;18:5836.
Nayar 1996
Nayar R, Lage JM. Placental changes in a first trimester
missed abortion in maternal systemic lupus erythematosus

with antiphospholipid syndrome; a case report and review


of the literature. Human Pathology 1996;27(2):2016.
Nicolaides 2006
Nicolaides KH, Bindra R, Turan OM, Chefetz I, Sammar
M, Meiri H, et al.A novel approach to first trimester
screening for early pre-eclampsia combining serum PP13 and Doppler ultrasound. Ultrasound in Obstetrics and
Gynecology 2006;27(1):137.
Olofsson 1993
Olofsson P, Laurini RN, Marsal K. A high uterine artery
pulsatility index reflects a defective development of
placental bed spiral arteries in pregnancies complicated by
hypertension and fetal growth retardation. European Journal
of Obstetrics & Gynecology and Reproductive Biology 1993;49
(3):1618.
Owen 2001
Owen P. Fetal assessment in the third trimester: fetal growth
and biophysical methods. In: Chamberlain G, Steer P
editor(s). Turnbulls obstetrics. 3rd Edition. Edinburgh:
Churchill Livingstone, 2001.
Papageorghiou 2001
Papageorghiou AT, Yu CK, Bindra R, Pandis G, Nicolaides
KH: Fetal Medicine Foundation Second Trimester
Screening Group. Multicenter screening for pre-eclampsia
and fetal growth restriction by transvaginal uterine artery
Doppler at 23 weeks of gestation. Ultrasound Obstetrics and
Gynecology 2001;18:4419.
Parra 2005
Parra M, Rodrigo R, Barja P, Bosco C, Fernndez V, Muoz
H, et al.Screening tests for preeclampsia through assessment
of uteroplacental blood flow and biochemical markers of
oxidative stress and endothelial dysfunction. American
Journal of Obstetrics and Gynecology 2005;193:148691.
Plasencia 2007
Plasencia W, Maiz N, Bonino S, Kaihura C, Nicolaides
KH. Uterine artery Doppler at 11+0 to 13+6 weeks in the
prediction of pre-eclampsia. Ultrasound in Obstetrics and
Gynecology 2007;30:7429.
RevMan 2008
The Nordic Cochrane Centre, The Cochrane Collaboration.
Review Manager (RevMan). 5.0. Copenhagen: The Nordic
Cochrane Centre, The Cochrane Collaboration, 2008.
Sibai 2005
Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet
2005;365:78599.
Spencer 2007
Spencer K, Cowans NJ, Chefetz I, Tal J, Meiri H. First
trimester maternal serum PP-13, PAPP-A and second
trimester uterine artery Doppler pulsatility index as marker
of pre-eclampsia. Ultrasound Obstetrics and Gynecology
2007;29:12834.
Von Dadelszen 2002
Von Dadelszen P, Magee LA. Could an infectious trigger
explain the differential maternal response to the shared
placental pathology of preeclampsia and normotensive

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

15

intrauterine growth restriction?. Acta Obstetricia et


Gynecologica Scandinavica 2002;81(7):6428.
Yu 2005
Yu CK, Smith GC, Papageorghiou AT, Cacho AM,
Nicolaides KH, Fetal Medicine Foundation Second
Trimester Screening Group. An integrated model for the
prediction of pre-eclampsia using maternal factors and
uterine artery Doppler velocimetry in unselected low-risk
women. American Journal of Obstetrics and Gynecology 2005;
193(2):42936.
Zhong 2010
Zhong Y, Tuuli M, Odibo AO. First trimester assessment of
placental function and the prediction of pre-eclampsia and
intrauterine growth restriction. Prenatal Diagnosis 2010;30:
293308.

Indicates the major publication for the study

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

16

CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID]


Goffinet 2001
Methods

Multicentre randomised trial. Stratified by centre and parity (nulliparous or multiparous)


. Blocks of 4. Randomisatioin numbers were established using tables of order 4 permutations
Individual woman.

Participants

Inclusion criteria:
All women attending for a routine antenatal visit before 24 weeks.
Nulliparaus and multiparus.
Low risk.
N = 3317, though analysis on 3133.
Exclusion criteria:
Women who had indications for UAD including chronic hypertension, diabetes,
previous fetal death, IUGR, hypertensive disorders of pregnancy.
Women known to be at high risk before 24 weeks did not enter the trial.
Women with contraindications to aspirin were also excluded.

Interventions

Experimental intervention: uterine artery Doppler US


Uterine artery Doppler performed between 20 and 24. 100 mg of aspirin daily
until the 35th week was prescribed to patients with abnormal results.
N = 1672 randomised though 100 lost to follow up = 1572.
Control/comparison intervention: no Doppler US
Women allocated to the control group did not have a uterine artery Doppler on
the day of the second-trimester abdominal US examination.
N = 1645 though 84 lost to follow up = 1561.

Outcomes

Principal outcome: IUGR (birthweight < 10% and < 3% according to gestational age)
Pre-eclampsia, gestational hypertension.
Uterine bleeding, oligohydramnios, abnormal CTG.
Number of antenatal consultations, days of antenatal hospitalisation, CTG
measurements, ultrasound and Doppler tests.
Peri and neonatal death, fetal distress defined by abnormal CTG resulting in
intervention (caesarean or instrumental delivery), Apgar score, neonatal resuscitation,
neonatal transfer.

Notes
Risk of bias
Item

Authors judgement

Description

Adequate sequence generation?

Yes

The randomisation was stratified


according to centre and parity (nulliparae
or multiparae).
The randomisation numbers were

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

17

Goffinet 2001

(Continued)

established using tables of order four


permutation.
Allocation concealment?

Yes

Randomisation procedure using


sealed envelopes.
The randomisation procedure was
verified by checking all unused envelopes
at the end of the trial and confirming that
envelopes had been used in ascending
order.

Blinding?
All outcomes

No

Not possible to blind.

Incomplete outcome data addressed?


All outcomes

Yes

Loss of participants to follow up at each


data collection point:
115 follow-up data missing.
Overall 100/1672 (6%) lost from
Doppler.
Overall 84/1765 (5%) lost from
control group.
Exclusion of participants after randomisation:
Shortly after randomisation, follow
up ceased for 69 women: 39 in Doppler
group and 30 in control group. Of those:
1. 48 (27 in Doppler and 21 in control)
follow up ended when verification of
admission criteria indicated that they
should not have been randomised.
2. 4 women refused further
participation after randomisation.
3. 6 had miscarriages before
ultrasound.

Free of selective reporting?

Unclear

We did not assess the trial protocol.

Free of other bias?

Unclear

2 centres stopped inclusions a few month


after the beginning of the study and did
not send the records of 11 women they had
included
Describe any baseline in balance: none
identified.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

18

Subtil 2003
Methods

Multicentre randomised controlled trial (12 centres). Block randomisation - blocks of 8


or 16, stratified by centre
Unit of randomisation: individual woman, 2:1 ratio for randomisation of Doppler vs
placebo
Part of a larger study (Essai Regional Aspirine Mere Enfant, ERASME trial) which
evaluated the routine prescription of low-dose aspirin (100mg) in nulliparous women

Participants

Inclusion criteria:
Nulliparae (no previous delivery 22 weeks) between 14 and 20+6 weeks.
Singletons and twins.
N = 1870. 2491 women agreed to participate and were randomised. 621 were
excluded from the current evaluation as they were allocated to routine aspirin leaving
1870 in the current evaluation. Data available on 1860 women.
Exclusion criteria:
No history of hypertension.
No clear indications for or contraindications to the prescription of aspirin or
another anticoagulant during the pregnancy.

Interventions

Experimental intervention: uterine artery Doppler US


Half underwent utero-placental artery Doppler at the same time as the secondtrimester anatomical ultrasound (22-24 weeks), with low-dose aspirin (100 mg)
prescribed only if the findings were abnormal until 36 weeks.
N = 1253 women (22 twin pregnancies). Outcomes on 1244 women and 1249
neonates.
Control/comparison intervention: no Doppler US
The other half (1238) was further divided randomly into 2 groups:
i) daily treatment with low-dose aspirin 100 mg (N = 621) excluded from the
current evaluation;
ii) or placebo until the end of 34 weeks (N = 617).
The group of patients receiving aspirin or placebo began treatment the day after
randomisation (between 14+1 and 21+0 weeks) and stopped after 34 weeks.
N = 617 women (14 twin pregnancies). Outcomes on 616 women and 627
neonates.

Outcomes

Pre-eclampsia, pregnancy related hypertension, very low or low birthweight for gestational age (birthweight 3rd and 10th centile of the standard curves used in France),
HELLP syndrome, placental abruption or a caesarean section because of fetal indication
(uncompensated maternal hypertension, suspected IUGR, meconium stained amniotic
fluid or placental abruption)

Notes

Doppler group included 22 twin pregnancies and the control group included 14 twin
pregnancies

Risk of bias
Item

Authors judgement

Description

Adequate sequence generation?

Yes

...a randomisation list was computer generated by the manufacturer of the treatment

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

19

Subtil 2003

(Continued)

boxes before the study began. Treatment


randomisation was balanced in blocks of 8
and stratified by centre. Each block of eight
box numbers was then randomly mixed,
according to a random number table, with
eight boxes labelled Doppler. The randomisation was thus balanced by blocks of
16 in these centres, and the box numbers
were not consecutive.
Allocation concealment?

Yes

...each patient was randomly allocated to a


group immediately after inclusion by connection to an always available server.... After verifying the inclusion criteria and the
patients consent, the server provided either a treatment box number or the word
Doppler to the physician investigator. At
the end of prenatal consultation the physician gave the patient a numbered treatment
box (neither the physician nor the patient
knew whether this was aspirin or placebo)
or an appointment (between 22 and 24
weeks) for a utero-placental artery Doppler.

Blinding?
All outcomes

No

It was not possible to blind participants and


clinicians with regard to the use of Doppler
US or not (and the outcome assessor would
often be the clinician), although participants and clinicians were blind to the use
of aspirin or placebo in women with abnormal Doppler US results

Incomplete outcome data addressed?


All outcomes

Yes

Loss of participants to follow up at each


data collection point:
9 women lost to follow up in the
Doppler group and 1 in the no Dopper
group. (0.7% to 0.2 = %, NS).
Exclusion of participants after randomisation:
2491 women agreed to participate
and were randomised. 621 were excluded
from the current evaluation as they were
allocated to routine aspirin (not included
in current evaluation). As the allocation to
aspirin was done by randomisation of the
no Doppler group, the randomisation
assessed in this comparison still stands.
Doppler not performed on 78 (6%)

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

20

Subtil 2003

(Continued)

women in Doppler group.


26 lost to follow up in Doppler
group of which 17 were ToP. In the
placebo group it was 4 of which 3 were
ToP.
Intention-to-treat analysis.
Free of selective reporting?

Unclear

We did not assess the trial protocol.

Free of other bias?

Yes

The study was not stopped early.


No baseline in balance:
no imbalances on: maternal age; low
educational level; smoking; height;
weight; BMI; systolic BP; diastolic BP;
gestational age at inclusion; multiple
pregnancy.

AFI: amniotic fluid index


BMI: basal metabolic rate
BP: blood pressure
CTG: cardiotocography
HELLP: haemolysis, elevated liver enzymes, low platelets
IUGR: intrauterine growth restriction
NS: not significant
ToP: termination of pregnancy
UAD: uterine artery Doppler
US: ultrasound

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Almstrom 1992

Study assessing umbilical artery Doppler ultrasound.

Ben-Ami 1995

This study is not randomised.

Biljan 1992

Study assessing umbilical artery Doppler ultrasound.

Burke 1992

Study assessing umbilical artery Doppler ultrasound.

Davies 1992

Study assessing umbilical artery and uterine artery Doppler ultrasound, see Alfirevic 2010b.

de Rochambeau 1992

Study assessing umbilical artery Doppler ultrasound.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

21

(Continued)

Doppler 1997

Study assessing umbilical artery Doppler ultrasound.

Giles 2003

Study assessing umbilical artery Doppler ultrasound with biometry

Gonsoulin 1991

Conference abstract - not clear whether high-risk/low-risk/unselected pregnancies, and no data suitable for
inclusion. Further details were sought from the authors by the authors of the previous Doppler for unselected
population review, without success.

Haley 1997

Study assessing umbilical artery Doppler ultrasound.

Hofmeyr 1991

Study assessing umbilical artery Doppler ultrasound.

Johnstone 1993

Study assessing umbilical artery Doppler ultrasound.

Mason 1993

Study assessing umbilical artery Doppler ultrasound.

McCowan 1996

Conference abstract only but outcomes were comparing women with normal and abnormal Doppler ultrasound readings, so not a randomised comparison

McParland 1988

This study has never been reported in full although it has been partly reported in a review article (McParland
1988) and a full manuscript has been given to the review authors by Dr Pearce, who has been accused of
publishing reports of trials whose veracity cannot be confirmed (BJOG 1995). Consequently, the Doppler
trial data are not now thought by the review authors to be sufficiently reliable to be retained within this
review.

Neales 1994

Study assessing umbilical artery Doppler ultrasound.

Newnham 1991

Study assessing umbilical artery and uterine artery Doppler ultrasound, see Alfirevic 2010a.

Newnham 1993

Study assessing umbilical artery and uterine artery Doppler ultrasound (see Alfirevic 2010b).

Nienhuis 1997

Study assessing umbilical artery Doppler ultrasound.

Nimrod 1992

Study assessing umbilical artery Doppler ultrasound.

Norman 1992

Study assessing umbilical artery Doppler ultrasound.

Omtzigt 1994

Study assessing umbilical artery Doppler ultrasound.

Pattinson 1994

Study assessing umbilical artery Doppler ultrasound.

Pearce 1992

Dr Pearce has been accused of publishing reports of trials whose veracity cannot be confirmed (BJOG 1995)
. Consequently, the Doppler trial data are not now thought by the review authors to be sufficiently reliable
to be retained within this review.

Schneider 1992

Conference abstract in English language identified - unexplained difference in numbers (250 vs 329) in
Doppler vs control groups suggesting allocation bias. The definitive publication after translation from Ger-

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

22

(Continued)

man did not explain this difference and failed to outline the trial methodology
Scholler 1993

This study was translated from German for us. It was a quasi-RCT of 211 women undergoing Doppler
ultrasound versus no Doppler ultrasound. It was excluded for a combination of the following reasons: the
only outcome relevant to our review was induction of labour; the study had high risk of bias being a quasiRCT; further information was needed from the authors before this data could be included. Data reported
for induction of labour: Doppler group 37/108 and no Doppler group 41/103

Trudinger 1987

Study assessing umbilical artery Doppler ultrasound.

Tyrrell 1990

Study assessing umbilical artery and uterine artery Doppler ultrasound, see Alfirevic 2010a.

Whittle 1994

Study assessing umbilical artery Doppler ultrasound.

Williams 2003

Study assessing umbilical artery Doppler ultrasound.

RCT: randomised controlled trial


vs: versus

Characteristics of studies awaiting assessment [ordered by study ID]


Ellwood 1997
Methods

Randomised controlled trial.


Individual woman.

Participants

Inclusion criteria
Pregnant women with no pre-existing medical condition.
First ongoing pregnancy (one first trimester pregnancy loss is allowed).
Exclusion criteria
Medical conditions, previous pregnancies.

Interventions

Experimental intervention: uterine artery Doppler


18-20 weeks: routine scan.
24-26 weeks: uterine artery Doppler waveform studies and transvaginal assessment of the cervix.
38 weeks: AFI assessment.
Control/comparison intervention: no uterine artery Doppler
Routine ultrasound at 18-20 weeks and other scans as clinically indicated.

Outcomes

Pre-specified outcomes: gestational age at delivery, rate of preterm birth, unplanned admissions for pre-eclampsia
and fetal growth restriction and bed days, neonates with Apgar scores < 7 at 5 min, neonatal admissions and special
care nursery bed days

Notes

The study was still ongoing when this report was written. The plan was to recruit 524 women, 262 in each group
(power calculation done on admission to neonatal nursery). At time of report 364 women had been randomised and
145 had given birth and been followed up

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

23

Ellwood 1997

(Continued)

We are trying to contact the authors for further information

Snaith 2006
Methods

Randomised controlled trial.

Participants

Low-risk primiparous women.

Interventions

Structured telephone support intervention provided by midwife +/- uterine artery Doppler screening

Outcomes

Primary outcome: number of antenatal contacts with health professionals


Secondary outcomes: number of antenatal admissions to hospital, anxiety, level of perceived social support, satisfaction
with care, economic evaluation, major clinical outcomes

Notes

Registered protocol: Current Controlled Trials (http://controlled-trials.com/mrct)


We are contacting the author for further information as this trial should have completed but we can find no publication

AFI: amniotic fluid index

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

24

DATA AND ANALYSES

Comparison 1. Uterine artery Doppler ultrasound versus no Doppler ultrasound, 1st trimester

Outcome or subgroup title


1 Any perinatal death after
randomisation
1.1 Women at increased risk
of complications
1.2 Women at low risk of
complications
1.3 Unselected population of
women
2 Hypertensive disorders
2.1 Women at increased risk
of complications
2.2 Women at low risk of
complications
2.3 Unselected population of
women
3 Stillbirth
3.1 Women at increased risk
of complications
3.2 Women at low risk of
complications
3.3 Unselected population of
women
4 Neonatal death
4.1 Women at increased risk
of complications
4.2 Women at low risk of
complications
4.3 Unselected population of
women
5 Any potentially preventable
perinatal death after
randomisation
5.1 Women at increased risk
of complications
5.2 Women at low risk of
complications
5.3 Unselected population of
women
6 Serious neonatal morbidity composite
6.1 Women at increased risk
of complications

No. of
studies

No. of
participants

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Statistical method

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Effect size

25

6.2 Women at low risk of


complications
6.3 Unselected population of
women
7 Intrauterine growth restriction
7.1 Women at increased risk
of complications
7.2 Women at low risk of
complications
7.3 Unselected population of
women
8 Fetal distress
8.1 Women at increased risk
of complications
8.2 Women at low risk of
complications
8.3 Unselected population of
women
9 Neonatal resuscitation
9.1 Women at increased risk
of complications
9.2 Women at low risk of
complications
9.3 Unselected population of
women
10 Infant requiring intubation/
ventilation
10.1 Women at increased risk
of complications
10.2 Women at low risk of
complications
10.3 Unselected population of
women
11 Infant respiratory distress
syndrome
11.1 Women at increased risk
of complications
11.2 Women at low risk of
complications
11.3 Unselected population of
women
12 Apgar score < 7 at 5 min
12.1 Women at increased risk
of complications
12.2 Women at low risk of
complications
12.3 Unselected population of
women
13 Neonatal admission to SCBU
or NICU

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

26

13.1 Women at increased risk


of complications
13.2 Women at low risk of
complications
13.3 Unselected population of
women
14 Spontaneous preterm birth (<
37 weeks)
14.1 Women at increased risk
of complications
14.2 Women at low risk of
complications
14.3 Unselected population of
women
15 Iatrogenic preterm birth (< 37
weeks)
15.1 Women at increased risk
of complications
15.2 Women at low risk of
complications
15.3 Unselected population of
women
16 Caesarean section (both elective
and emergency)
16.1 Women at increased risk
of complications
16.2 Women at low risk of
complications
16.3 Unselected population of
women
17 Elective caesarean section
17.1 Women at increased risk
of complications
17.2 Women at low risk of
complications
17.3 Unselected population of
women
18 Emergency caesarean section
18.1 Women at increased risk
of complications
18.2 Women at low risk of
complications
18.3 Unselected population of
women
19 Serious maternal morbidity and
mortality
19.1 Women at increased risk
of complications
19.2 Women at low risk of
complications

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

27

19.3 Unselected population of


women
20 Mothers admission to special
care or intensive care unit
20.1 Women at increased risk
of complications
20.2 Women at low risk of
complications
20.3 Unselected population of
women
21 Gestational age at birth
21.1 Women at increased risk
of complications
21.2 Women at low risk of
complications
21.3 Unselected population of
women
22 Infant birthweight
22.1 Women at increased risk
of complications
22.2 Women at low risk of
complications
22.3 Unselected population of
women
23 Length of infant hospital stay
23.1 Women at increased risk
of complications
23.2 Women at low risk of
complications
23.3 Unselected population of
women
24 Length of maternal hospital
stay
24.1 Women at increased risk
of complications
24.2 Women at low risk of
complications
24.3 Unselected population of
women

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

0
0

0
0

Mean Difference (IV, Fixed, 95% CI)


Mean Difference (IV, Fixed, 95% CI)

Not estimable
Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

0
0

0
0

Mean Difference (IV, Fixed, 95% CI)


Mean Difference (IV, Fixed, 95% CI)

Not estimable
Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

0
0

0
0

Mean Difference (IV, Fixed, 95% CI)


Mean Difference (IV, Fixed, 95% CI)

Not estimable
Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Comparison 2. Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester

Outcome or subgroup title


1 Any perinatal death after
randomisation

No. of
studies

No. of
participants

5009

Statistical method
Risk Ratio (M-H, Random, 95% CI)

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Effect size
1.61 [0.48, 5.39]
28

1.1 Women at increased risk


of complications
1.2 Women at low risk of
complications
1.3 Unselected population of
women
2 Hypertensive disorders
2.1 Women at increased risk
of complications
2.2 Women at low risk of
complications
2.3 Unselected population of
women
3 Stillbirth
3.1 Women at increased risk
of complications
3.2 Women at low risk of
complications
3.3 Unselected population of
women
4 Neonatal death
4.1 Women at increased risk
of complications
4.2 Women at low risk of
complications
4.3 Unselected population of
women
5 Any potentially preventable
perinatal death after
randomisation
5.1 Women at increased risk
of complications
5.2 Women at low risk of
complications
5.3 Unselected population of
women
6 Serious neonatal morbidity composite
6.1 Women at increased risk
of complications
6.2 Women at low risk of
complications
6.3 Unselected population of
women
7 Intrauterine growth restriction
7.1 Women at increased risk
of complications
7.2 Women at low risk of
complications
7.3 Unselected population of
women

Risk Ratio (M-H, Random, 95% CI)

Not estimable

5009

Risk Ratio (M-H, Random, 95% CI)

1.61 [0.48, 5.39]

Risk Ratio (M-H, Random, 95% CI)

Not estimable

2
0

4987
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

1.08 [0.87, 1.33]


Not estimable

4987

Risk Ratio (M-H, Fixed, 95% CI)

1.08 [0.87, 1.33]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

2
0

5003
0

Risk Ratio (M-H, Random, 95% CI)


Risk Ratio (M-H, Random, 95% CI)

1.44 [0.38, 5.49]


Not estimable

5003

Risk Ratio (M-H, Random, 95% CI)

1.44 [0.38, 5.49]

Risk Ratio (M-H, Random, 95% CI)

Not estimable

2
0

5009
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

2.39 [0.39, 14.83]


Not estimable

5009

Risk Ratio (M-H, Fixed, 95% CI)

2.39 [0.39, 14.83]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

5009

Risk Ratio (M-H, Random, 95% CI)

1.29 [0.21, 7.94]

Risk Ratio (M-H, Random, 95% CI)

Not estimable

5009

Risk Ratio (M-H, Random, 95% CI)

1.29 [0.21, 7.94]

Risk Ratio (M-H, Random, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

2
0

5006
0

Odds Ratio (M-H, Random, 95% CI)


Odds Ratio (M-H, Random, 95% CI)

0.98 [0.64, 1.50]


Not estimable

5006

Odds Ratio (M-H, Random, 95% CI)

0.98 [0.64, 1.50]

Odds Ratio (M-H, Random, 95% CI)

Not estimable

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

29

8 Fetal distress
8.1 Women at increased risk
of complications
8.2 Women at low risk of
complications
8.3 Unselected population of
women
9 Neonatal resuscitation
9.1 Women at increased risk
of complications
9.2 Women at low risk of
complications
9.3 Unselected population of
women
10 Infant requiring intubation/
ventilation
10.1 Women at increased risk
of complications
10.2 Women at low risk of
complications
10.3 Unselected population of
women
11 Infant respiratory distress
syndrome
11.1 Women at increased risk
of complications
11.2 Women at low risk of
complications
11.3 Unselected population of
women
12 Apgar score < 7 at 5 min
12.1 Women at increased risk
of complications
12.2 Women at low risk of
complications
12.3 Unselected population of
women
13 Neonatal admission to SCBU
or NICU
13.1 Women at increased risk
of complications
13.2 Women at low risk of
complications
13.3 Unselected population of
women
14 Spontaneous preterm birth (<
37 weeks)
14.1 Women at increased risk
of complications

0
0

0
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

Not estimable
Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

1
0

3133
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

0.94 [0.75, 1.19]


Not estimable

3133

Risk Ratio (M-H, Fixed, 95% CI)

0.94 [0.75, 1.19]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

1
0

3133
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

1.08 [0.48, 2.45]


Not estimable

3133

Risk Ratio (M-H, Fixed, 95% CI)

1.08 [0.48, 2.45]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

5001

Risk Ratio (M-H, Fixed, 95% CI)

1.12 [0.92, 1.37]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

5001

Risk Ratio (M-H, Fixed, 95% CI)

1.12 [0.92, 1.37]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

30

14.2 Women at low risk of


complications
14.3 Unselected population of
women
15 Iatrogenic preterm birth (< 37
weeks)
15.1 Women at increased risk
of complications
15.2 Women at low risk of
complications
15.3 Unselected population of
women
16 Caesarean section (both elective
and emergency)
16.1 Women at increased risk
of complications
16.2 Women at low risk of
complications
16.3 Unselected population of
women
17 Elective caesarean section
17.1 Women at increased risk
of complications
17.2 Women at low risk of
complications
17.3 Unselected population of
women
18 Emergency caesarean section
18.1 Women at increased risk
of complications
18.2 Women at low risk of
complications
18.3 Unselected population of
women
19 Serious maternal morbidity and
mortality
19.1 Women at increased risk
of complications
19.2 Women at low risk of
complications
19.3 Unselected population of
women
20 Mothers admission to special
care or intensive care unit
20.1 Women at increased risk
of complications
20.2 Women at low risk of
complications
20.3 Unselected population of
women
21 Gestational age at birth

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

4982

Risk Ratio (M-H, Random, 95% CI)

0.92 [0.51, 1.65]

Risk Ratio (M-H, Random, 95% CI)

Not estimable

4982

Risk Ratio (M-H, Random, 95% CI)

0.92 [0.51, 1.65]

Risk Ratio (M-H, Random, 95% CI)

Not estimable

3133

Risk Ratio (M-H, Fixed, 95% CI)

1.09 [0.91, 1.29]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

3133

Risk Ratio (M-H, Fixed, 95% CI)

1.09 [0.91, 1.29]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

1
0

3133
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

1.05 [0.82, 1.34]


Not estimable

3133

Risk Ratio (M-H, Fixed, 95% CI)

1.05 [0.82, 1.34]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

1
0

3133
0

Risk Ratio (M-H, Fixed, 95% CI)


Risk Ratio (M-H, Fixed, 95% CI)

1.13 [0.87, 1.46]


Not estimable

3133

Risk Ratio (M-H, Fixed, 95% CI)

1.13 [0.87, 1.46]

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

Risk Ratio (M-H, Fixed, 95% CI)

Not estimable

3133

Mean Difference (IV, Fixed, 95% CI)

-0.10 [-0.24, 0.04]

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

31

21.1 Women at increased risk


of complications
21.2 Women at low risk of
complications
21.3 Unselected population of
women
22 Infant birthweight
22.1 Women at increased risk
of complications
22.2 Women at low risk of
complications
22.3 Unselected population of
women
23 Length of infant hospital stay
23.1 Women at increased risk
of complications
23.2 Women at low risk of
complications
23.3 Unselected population of
women
24 Length of maternal hospital
stay
24.1 Women at increased risk
of complications
24.2 Women at low risk of
complications
24.3 Unselected population of
women

Mean Difference (IV, Fixed, 95% CI)

Not estimable

3133

Mean Difference (IV, Fixed, 95% CI)

-0.10 [-0.24, 0.04]

Mean Difference (IV, Fixed, 95% CI)

Not estimable

1
0

3133
0

Mean Difference (IV, Fixed, 95% CI)


Mean Difference (IV, Fixed, 95% CI)

-34.0 [-68.63, 0.63]


Not estimable

3133

Mean Difference (IV, Fixed, 95% CI)

-34.0 [-68.63, 0.63]

Mean Difference (IV, Fixed, 95% CI)

Not estimable

0
0

0
0

Mean Difference (IV, Fixed, 95% CI)


Mean Difference (IV, Fixed, 95% CI)

Not estimable
Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Mean Difference (IV, Fixed, 95% CI)

Not estimable

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

32

Analysis 2.1. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 1 Any perinatal death after randomisation.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 1 Any perinatal death after randomisation

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio
MH,Random,95%
CI

Weight

Risk Ratio
MH,Random,95%
CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

13/1572

14/1561

54.6 %

0.92 [ 0.43, 1.96 ]

Subtil 2003

25/1249

4/627

45.4 %

3.14 [ 1.10, 8.98 ]

2821

2188

100.0 %

1.61 [ 0.48, 5.39 ]

0.0 %

0.0 [ 0.0, 0.0 ]

2188

100.0 %

1.61 [ 0.48, 5.39 ]

Subtotal (95% CI)

Total events: 38 (Doppler US), 18 (No Doppler US)


Heterogeneity: Tau2 = 0.55; Chi2 = 3.54, df = 1 (P = 0.06); I2 =72%
Test for overall effect: Z = 0.77 (P = 0.44)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

2821

Total events: 38 (Doppler US), 18 (No Doppler US)


Heterogeneity: Tau2 = 0.55; Chi2 = 3.54, df = 1 (P = 0.06); I2 =72%
Test for overall effect: Z = 0.77 (P = 0.44)

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

33

Analysis 2.2. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 2 Hypertensive disorders.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 2 Hypertensive disorders

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio
M-H,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

83/1572

81/1561

51.2 %

1.02 [ 0.76, 1.37 ]

133/1238

58/616

48.8 %

1.14 [ 0.85, 1.53 ]

2810

2177

100.0 %

1.08 [ 0.87, 1.33 ]

0.0 %

0.0 [ 0.0, 0.0 ]

2177

100.0 %

1.08 [ 0.87, 1.33 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001
Subtil 2003

Subtotal (95% CI)

Total events: 216 (Doppler US), 139 (No Doppler US)


Heterogeneity: Chi2 = 0.29, df = 1 (P = 0.59); I2 =0.0%
Test for overall effect: Z = 0.70 (P = 0.48)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

2810

Total events: 216 (Doppler US), 139 (No Doppler US)


Heterogeneity: Chi2 = 0.29, df = 1 (P = 0.59); I2 =0.0%
Test for overall effect: Z = 0.70 (P = 0.48)

0.5

0.7

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

1.5

Favours no Doppler

34

Analysis 2.3. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 3 Stillbirth.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 3 Stillbirth

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio
MH,Random,95%
CI

Weight

Risk Ratio
MH,Random,95%
CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Subtil 2003

24/1253

4/617

47.0 %

2.95 [ 1.03, 8.48 ]

Goffinet 2001

10/1572

13/1561

53.0 %

0.76 [ 0.34, 1.74 ]

2825

2178

100.0 %

1.44 [ 0.38, 5.49 ]

0.0 %

0.0 [ 0.0, 0.0 ]

2178

100.0 %

1.44 [ 0.38, 5.49 ]

Subtotal (95% CI)

Total events: 34 (Doppler US), 17 (No Doppler US)


Heterogeneity: Tau2 = 0.70; Chi2 = 4.02, df = 1 (P = 0.04); I2 =75%
Test for overall effect: Z = 0.54 (P = 0.59)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

2825

Total events: 34 (Doppler US), 17 (No Doppler US)


Heterogeneity: Tau2 = 0.70; Chi2 = 4.02, df = 1 (P = 0.04); I2 =75%
Test for overall effect: Z = 0.54 (P = 0.59)

0.05

0.2

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

20

Favours no Doppler

35

Analysis 2.4. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 4 Neonatal death.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 4 Neonatal death

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio
M-H,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

3/1572

1/1561

60.1 %

2.98 [ 0.31, 28.61 ]

Subtil 2003

1/1249

0/627

39.9 %

1.51 [ 0.06, 36.94 ]

2821

2188

100.0 %

2.39 [ 0.39, 14.83 ]

0.0 %

0.0 [ 0.0, 0.0 ]

2188

100.0 %

2.39 [ 0.39, 14.83 ]

Subtotal (95% CI)

Total events: 4 (Doppler US), 1 (No Doppler US)


Heterogeneity: Chi2 = 0.12, df = 1 (P = 0.73); I2 =0.0%
Test for overall effect: Z = 0.94 (P = 0.35)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

2821

Total events: 4 (Doppler US), 1 (No Doppler US)


Heterogeneity: Chi2 = 0.12, df = 1 (P = 0.73); I2 =0.0%
Test for overall effect: Z = 0.94 (P = 0.35)

0.01

0.1

Favours Doppler

10

100

Favours no Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

36

Analysis 2.5. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 5 Any potentially preventable perinatal death after randomisation.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 5 Any potentially preventable perinatal death after randomisation

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio
MH,Random,95%
CI

Weight

Risk Ratio
MH,Random,95%
CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

5/1572

8/1561

61.0 %

0.62 [ 0.20, 1.89 ]

Subtil 2003

8/1249

1/627

39.0 %

4.02 [ 0.50, 32.04 ]

2821

2188

100.0 %

1.29 [ 0.21, 7.94 ]

0.0 %

0.0 [ 0.0, 0.0 ]

2188

100.0 %

1.29 [ 0.21, 7.94 ]

Subtotal (95% CI)

Total events: 13 (Doppler US), 9 (No Doppler US)


Heterogeneity: Tau2 = 1.09; Chi2 = 2.51, df = 1 (P = 0.11); I2 =60%
Test for overall effect: Z = 0.27 (P = 0.79)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

2821

Total events: 13 (Doppler US), 9 (No Doppler US)


Heterogeneity: Tau2 = 1.09; Chi2 = 2.51, df = 1 (P = 0.11); I2 =60%
Test for overall effect: Z = 0.27 (P = 0.79)

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

37

Analysis 2.7. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 7 Intrauterine growth restriction.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 7 Intrauterine growth restriction

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Odds Ratio
MH,Random,95%
CI

Weight

Odds Ratio
MH,Random,95%
CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

162/1572

135/1561

51.1 %

1.21 [ 0.95, 1.54 ]

Subtil 2003

158/1246

98/627

48.9 %

0.78 [ 0.60, 1.03 ]

2818

2188

100.0 %

0.98 [ 0.64, 1.50 ]

0.0 %

0.0 [ 0.0, 0.0 ]

2188

100.0 %

0.98 [ 0.64, 1.50 ]

Subtotal (95% CI)

Total events: 320 (Doppler US), 233 (No Doppler US)


Heterogeneity: Tau2 = 0.08; Chi2 = 5.57, df = 1 (P = 0.02); I2 =82%
Test for overall effect: Z = 0.09 (P = 0.93)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

2818

Total events: 320 (Doppler US), 233 (No Doppler US)


Heterogeneity: Tau2 = 0.08; Chi2 = 5.57, df = 1 (P = 0.02); I2 =82%
Test for overall effect: Z = 0.09 (P = 0.93)

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

38

Analysis 2.9. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 9 Neonatal resuscitation.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 9 Neonatal resuscitation

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio
M-H,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

127/1572

134/1561

100.0 %

0.94 [ 0.75, 1.19 ]

1572

1561

100.0 %

0.94 [ 0.75, 1.19 ]

0.0 %

0.0 [ 0.0, 0.0 ]

1561

100.0 %

0.94 [ 0.75, 1.19 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

Subtotal (95% CI)

Total events: 127 (Doppler US), 134 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.51 (P = 0.61)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

1572

Total events: 127 (Doppler US), 134 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.51 (P = 0.61)
Test for subgroup differences: Not applicable

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

39

Analysis 2.12. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 12 Apgar score < 7 at 5 min.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 12 Apgar score < 7 at 5 min

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio
M-H,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

12/1572

11/1561

100.0 %

1.08 [ 0.48, 2.45 ]

1572

1561

100.0 %

1.08 [ 0.48, 2.45 ]

0.0 %

0.0 [ 0.0, 0.0 ]

1561

100.0 %

1.08 [ 0.48, 2.45 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

Subtotal (95% CI)

Total events: 12 (Doppler US), 11 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.19 (P = 0.85)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

1572

Total events: 12 (Doppler US), 11 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.19 (P = 0.85)
Test for subgroup differences: Not applicable

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

40

Analysis 2.13. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 13 Neonatal admission to SCBU or NICU.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 13 Neonatal admission to SCBU or NICU

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio
M-H,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

142/1572

121/1561

74.0 %

1.17 [ 0.92, 1.47 ]

63/1242

32/626

26.0 %

0.99 [ 0.66, 1.50 ]

2814

2187

100.0 %

1.12 [ 0.92, 1.37 ]

0.0 %

0.0 [ 0.0, 0.0 ]

2187

100.0 %

1.12 [ 0.92, 1.37 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001
Subtil 2003

Subtotal (95% CI)

Total events: 205 (Doppler US), 153 (No Doppler US)


Heterogeneity: Chi2 = 0.44, df = 1 (P = 0.51); I2 =0.0%
Test for overall effect: Z = 1.10 (P = 0.27)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

2814

Total events: 205 (Doppler US), 153 (No Doppler US)


Heterogeneity: Chi2 = 0.44, df = 1 (P = 0.51); I2 =0.0%
Test for overall effect: Z = 1.10 (P = 0.27)

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

41

Analysis 2.15. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 15 Iatrogenic preterm birth (< 37 weeks).
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 15 Iatrogenic preterm birth (< 37 weeks)

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio
MH,Random,95%
CI

Weight

Risk Ratio
MH,Random,95%
CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

16/1572

24/1561

46.3 %

0.66 [ 0.35, 1.24 ]

Subtil 2003

44/1237

18/612

53.7 %

1.21 [ 0.70, 2.07 ]

2809

2173

100.0 %

0.92 [ 0.51, 1.65 ]

0.0 %

0.0 [ 0.0, 0.0 ]

2173

100.0 %

0.92 [ 0.51, 1.65 ]

Subtotal (95% CI)

Total events: 60 (Doppler US), 42 (No Doppler US)


Heterogeneity: Tau2 = 0.09; Chi2 = 2.03, df = 1 (P = 0.15); I2 =51%
Test for overall effect: Z = 0.30 (P = 0.77)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

2809

Total events: 60 (Doppler US), 42 (No Doppler US)


Heterogeneity: Tau2 = 0.09; Chi2 = 2.03, df = 1 (P = 0.15); I2 =51%
Test for overall effect: Z = 0.30 (P = 0.77)

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

42

Analysis 2.16. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 16 Caesarean section (both elective and emergency).
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 16 Caesarean section (both elective and emergency)

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio
M-H,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

232/1572

212/1561

100.0 %

1.09 [ 0.91, 1.29 ]

1572

1561

100.0 %

1.09 [ 0.91, 1.29 ]

0.0 %

0.0 [ 0.0, 0.0 ]

1561

100.0 %

1.09 [ 0.91, 1.29 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

Subtotal (95% CI)

Total events: 232 (Doppler US), 212 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.94 (P = 0.35)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

1572

Total events: 232 (Doppler US), 212 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.94 (P = 0.35)
Test for subgroup differences: Not applicable

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

43

Analysis 2.17. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 17 Elective caesarean section.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 17 Elective caesarean section

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio
M-H,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

117/1572

111/1561

100.0 %

1.05 [ 0.82, 1.34 ]

1572

1561

100.0 %

1.05 [ 0.82, 1.34 ]

0.0 %

0.0 [ 0.0, 0.0 ]

1561

100.0 %

1.05 [ 0.82, 1.34 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

Subtotal (95% CI)

Total events: 117 (Doppler US), 111 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.36 (P = 0.72)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

1572

Total events: 117 (Doppler US), 111 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.36 (P = 0.72)
Test for subgroup differences: Not applicable

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

44

Analysis 2.18. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 18 Emergency caesarean section.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 18 Emergency caesarean section

Study or subgroup

Doppler US

No Doppler US

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio
M-H,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

115/1572

101/1561

100.0 %

1.13 [ 0.87, 1.46 ]

1572

1561

100.0 %

1.13 [ 0.87, 1.46 ]

0.0 %

0.0 [ 0.0, 0.0 ]

1561

100.0 %

1.13 [ 0.87, 1.46 ]

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

Subtotal (95% CI)

Total events: 115 (Doppler US), 101 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.93 (P = 0.35)
3 Unselected population of women

Subtotal (95% CI)

Total events: 0 (Doppler US), 0 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: not applicable

Total (95% CI)

1572

Total events: 115 (Doppler US), 101 (No Doppler US)


Heterogeneity: not applicable
Test for overall effect: Z = 0.93 (P = 0.35)
Test for subgroup differences: Not applicable

0.01

0.1

Favours Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

100

Favours no Doppler

45

Analysis 2.21. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 21 Gestational age at birth.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 21 Gestational age at birth

Study or subgroup

Doppler US
N

Mean
Difference

No Doppler US
Mean(SD)

Mean(SD)

Weight

IV,Fixed,95% CI

Mean
Difference
IV,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

100.0 %

-0.10 [ -0.24, 0.04 ]

Heterogeneity: not applicable


Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

Subtotal (95% CI)

1572

1572

39 (2)

1561

39.1 (2)

100.0 % -0.10 [ -0.24, 0.04 ]

1561

Heterogeneity: not applicable


Test for overall effect: Z = 1.40 (P = 0.16)
3 Unselected population of women

Subtotal (95% CI)

1572

1561

0.0 %

0.0 [ 0.0, 0.0 ]

Heterogeneity: not applicable


Test for overall effect: not applicable

Total (95% CI)

100.0 % -0.10 [ -0.24, 0.04 ]

Heterogeneity: not applicable


Test for overall effect: Z = 1.40 (P = 0.16)
Test for subgroup differences: Not applicable

-100

-50

Favours no Doppler

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

50

100

Favours Doppler

46

Analysis 2.22. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd
trimester, Outcome 22 Infant birthweight.
Review:

Utero-placental Doppler ultrasound for improving pregnancy outcome

Comparison: 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
Outcome: 22 Infant birthweight

Study or subgroup

Doppler US

Mean
Difference

No Doppler US

Mean(SD)

Mean(SD)

Weight

IV,Fixed,95% CI

Mean
Difference
IV,Fixed,95% CI

1 Women at increased risk of complications

Subtotal (95% CI)

0.0 %

0.0 [ 0.0, 0.0 ]

100.0 %

-34.00 [ -68.63, 0.63 ]

Heterogeneity: not applicable


Test for overall effect: not applicable
2 Women at low risk of complications
Goffinet 2001

Subtotal (95% CI)

1572

3282 (503)

1572

1561

3316 (486)

100.0 % -34.00 [ -68.63, 0.63 ]

1561

Heterogeneity: not applicable


Test for overall effect: Z = 1.92 (P = 0.054)
3 Unselected population of women

Subtotal (95% CI)

1572

1561

0.0 %

0.0 [ 0.0, 0.0 ]

Heterogeneity: not applicable


Test for overall effect: not applicable

Total (95% CI)

100.0 % -34.00 [ -68.63, 0.63 ]

Heterogeneity: not applicable


Test for overall effect: Z = 1.92 (P = 0.054)
Test for subgroup differences: Not applicable

-100

-50

Favours no Doppler

50

100

Favours Doppler

HISTORY
Protocol first published: Issue 2, 2010
Review first published: Issue 9, 2010

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

47

CONTRIBUTIONS OF AUTHORS
T Stampalija drafted the background section and Z Alfirevic added further suggestions. G Gyte drafted the methodology section. T
Stampalija and G Gyte decided on the studies to include and extracted the data. T Stampalija entered the data into RevMan (RevMan
2008) and G Gyte checked this. T Stampalija drafted the text of the findings and all authors agreed with the final version of the review.

DECLARATIONS OF INTEREST
No known conflicts of interest.

SOURCES OF SUPPORT
Internal sources
The University of Liverpool, UK.

External sources
National Institute for Health Research, UK.
NIHR NHS Cochrane Collaboration Programme Grant Scheme award for NHS-prioritised centrally-managed, pregnancy and
childbirth systematic reviews: CPGS02

DIFFERENCES BETWEEN PROTOCOL AND REVIEW


There were no differences between the protocol and review.

INDEX TERMS
Medical Subject Headings (MeSH)
Pregnancy Outcome; Aspirin [administration & dosage]; Fibrinolytic Agents [administration & dosage]; Placenta [ ultrasonography];
Platelet Aggregation Inhibitors [administration & dosage]; Pregnancy Trimester, Second; Randomized Controlled Trials as Topic;
Regional Blood Flow; Ultrasonography, Prenatal; Uterine Artery [ ultrasonography]

MeSH check words


Female; Humans; Pregnancy

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review)


Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

48