Utero Placental Doppler Ultrasound For Improving Pregnancy Outcome Review PDF

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Analysis 2.1. Comparison 2 Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester, Outcome 1
Any perinatal death after randomisation. . . . . . . . . . . . . . . . . . . . . . . . . 33
Hypertensive disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Stillbirth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Neonatal death. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Any potentially preventable perinatal death after randomisation. . . . . . . . . . . . . . . . . 37
Intrauterine growth restriction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Neonatal resuscitation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Apgar score < 7 at 5 min. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Neonatal admission to SCBU or NICU. . . . . . . . . . . . . . . . . . . . . . . . . 41
Iatrogenic preterm birth (< 37 weeks). . . . . . . . . . . . . . . . . . . . . . . . . . 42
Caesarean section (both elective and emergency). . . . . . . . . . . . . . . . . . . . . . 43
Elective caesarean section. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Emergency caesarean section. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Gestational age at birth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Infant birthweight. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 48
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) i

[Intervention Review]
Utero-placental Doppler ultrasound for improving pregnancy

outcome
Tamara Stampalija1 , Gillian ML Gyte2 , Zarko Alfirevic3
1 Department of Obstetrics and Gynaecology, Children’s 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, Children’s 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.
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 utero-
placental 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 Group’s 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) 1
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 mother’s 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 mother’s 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 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.
Description of the condition The failure to undergo these physiologic vascular changes has
The blood supply to the uterus is provided mainly by the uterine been associated not just with pre-eclampsia (Brosens 1972; Khong
arteries and also by the ovarian arteries. Once the arterial vessels 1991; Sibai 2005; Von Dadelszen 2002) and intrauterine growth
reach myometrium, they divide into arcuate arteries, then into restriction (IUGR) (Bernstein 2000; Fisk 2001; Khong 1991), but
the radial arteries which ultimately branch into the spiral arteries. also with other maternal diseases such as diabetes mellitus (Khong
During the first and second trimester of pregnancy, trophoblast 1991), lupus erythematosus (Nayar 1996), antiphospholipid an-
invades the spiral arteries - a process that is fundamental for normal tibody syndrome (Levy 1998) and others (Barker 2004).
placentation. The most important change, but not the only one,
Description of the intervention from 80% to 85% for severe pre-eclampsia, requiring delivery be-
fore 34 weeks (Papageorghiou 2001; Yu 2005) and 90% for severe
Doppler ultrasound velocimetry uses the Doppler principle to
pre-eclampsia indicating delivery before 32 weeks (Papageorghiou
analyse the properties of the blood flow in a vessel of interest. This
2001).
physical principle explains the observed change in wave frequency
More recently, the interest for uterine artery measurements has
relative to the speed of a moving object. In case of Doppler ul-
moved from the second to the first trimester of pregnancy (13+6
trasound, the emitted ultrasound frequency will change when ul-
to 11+0 weeks of gestation). The rationale of measuring the uter-
trasound beam encounters moving blood. The principle can be
ine artery Doppler in the first trimester is the possibility to in-
applied using different ultrasound modalities such as continuous-
tervene with some prophylactic therapy such as antithrombotic
wave Doppler, pulsed-wave Doppler, colour and power Doppler
drugs while the trophoblastic invasion is still ongoing. The uterine
wave (Burns 1993; Chen 1996; Owen 2001). While colour and
artery Doppler has been found to be less predictive when compared
power Doppler provide visualisation of the blood flow and its di-
with the second trimester examination. Reported detection rate
rection, pulsed Doppler allows reproducible measurements of the
for uterine artery Doppler alone in the first trimester ranged from
blood velocities. The measurements obtained will reflect, in any
40% to 67% for early onset pre-eclampsia and 15% to 20% for late
vessel studied, the cardiac contraction force, density of the blood,
onset pre-eclampsia (Martin 2001; Parra 2005). In the attempt to
vessel wall elasticity, but more importantly peripheral and down-
improve the performance of the uterine artery as a screening test,
stream resistance (Owen 2001).
new algorithms that take into account the maternal characteristics,
Physiological process of the trophoblastic invasion of spiral arter-
history and/or biochemical markers have been proposed. In fact,
ies takes place between six and 24 weeks of gestation in normal
uterine artery Doppler in the first and second trimester, in com-
pregnancies. The blood flow from the uterine arteries to the pla-
bination with several biochemical markers, has been extensively
centa will progressively increase during that time. By studying the
tested as a predictive test for pre-eclampsia and IUGR, and the first
uterine arteries with pulse Doppler ultrasound, it is possible to as-
results are encouraging (Nicolaides 2006; Parra 2005; Plasencia
sess the progressive decrease in resistance to blood flow. The ratio-
2007; Spencer 2007; Zhong 2010). Nevertheless, at present the
nale of using the Doppler velocimetry of uterine arteries to assess
literature comprises several large uncontrolled cohort studies and
the failure of the placentation is related to fact that the lack of
as yet there are no randomised studies in this field, and the cost-
physiological transformation of the spiral arteries will cause high
effectiveness remains to be proven.
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-eclamp-
How the intervention might work
sia and IUGR (Cnossen 2008). The most commonly used indices
are the pulsatility and resistant index (PI and RI) which showed It is hoped that early detection of abnormal placental vascula-
the highest predictive value (Cnossen 2008). The qualitative de- ture, before maternal and fetal complications develop, would al-
scription focuses on the presence or absence of early diastolic notch low preventative interventions and more targeted maternal and
that could be either unilateral or bilateral. fetal surveillance. Low-dose aspirin is an example of a preventative
The abnormal findings in uterine arteries are usually defined as PI intervention that could be targeted to those with abnormal utero-
or RI above the 95 percentile at a given gestational age (Albaiges placental Doppler (Askie 2007).
2000; Bower 1993) and the presence of notching (a qualitative as-
sessment of flow velocity waveform - Harrington 1996). Numer-
ous studies have linked the high impedance and bilateral notching
in uterine arteries to early onset pre-eclampsia, IUGR and higher Why it is important to do this review
perinatal mortality (Aardema 2001; Albaiges 2000; Bower 1993; Doppler ultrasound has become an integral part of obstetric care
Harrington 1996; Olofsson 1993). (Alfirevic 2010a) and more clinicians are being trained to use it.
Reported sensitivity and detection rate of the uterine artery Using a non-invasive and relatively easy screening tool such as
Doppler to predict pre-eclampsia in unselected population range Doppler ultrasound of the uterine arteries to predict pre-eclamp-
from 50% to 60%, meaning that only half of the women that sia and IUGR is undoubtedly appealing. Early recognition of pre-
subsequently develop the disease will be correctly identified by the eclampsia and IUGR could improve maternal and perinatal out-
increased resistance in uterine arteries. On the other hand the re- come by administration antiplatelet therapy, appropriate antihy-
ported specificity is around 95%, which means that most women pertensive therapy, medication for fetal lung maturation and early
with normal uterine artery Doppler will not develop pre-eclamp- delivery. Nevertheless, labelling woman as ’at risk’ could cause sig-
sia. The performance of uterine artery Doppler as a screening test nificant anxiety and increase the number of unnecessary examina-
is higher when pre-eclampsia is divided in severe or early onset and tions and interventions (blood tests, hospital admission and pos-
mild or late onset pre-eclampsia. In that case, the sensitivity rises sibly early delivery).

This review will complement two other Cochrane reviews that revealed versus Doppler of utero-placental vessels concealed) in
focus on the fetal and umbilical Doppler ultrasound in high- first trimester of pregnancy.
risk populations (Alfirevic 2010a), and in low-risk populations 2. Doppler ultrasound of utero-placental vessels versus no
(Alfirevic 2010b). 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
OBJECTIVES
utero-placental vessels versus other types of Doppler ultrasound
To assess whether the use of utero-placental Doppler ultrasound of utero-placental vessels in first trimester of pregnancy.
(uterine arteries and placental vessels) improves the outcome of 4. Comparison of different forms of Doppler ultrasound of
low- and high-risk pregnancies. 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
METHODS 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
Criteria for considering studies for this review pregnancy.
Types of studies Types of outcome measures
All randomised trials and quasi-randomised studies comparing

utero-placental Doppler ultrasound (uterine, arcuate, radial and Primary outcomes
spiral arteries) in low- and high-risk pregnancies. We planned to
1. Any perinatal death after randomisation.
perform sensitivity analysis by trial quality. We included study
2. Hypertensive disorders (pre-eclampsia, eclampsia,
abstracts. We have considered cluster trials, though we found none,
haemolysis elevated liver enzymes and low platelets, chronic
but we did not think cross-over trials would be suitable for this
hypertension).
topic.
Secondary outcomes
Types of participants
1. Stillbirth (as defined by trialists).
Pregnant women, considered to be either low- or high-risk, who 2. Neonatal death (as defined by trialists).
had utero-placental Doppler ultrasound performed at first or sec- 3. Any potentially preventable perinatal death.*
ond trimester of pregnancy. We planned to include twin preg- 4. Serious neonatal morbidity - composite outcome including
nancies and to perform subgroup analysis for that population but hypoxic Ischaemic encephalopathy, intraventricular
there were insufficient data. haemorrhage, bronchopulmonary dysplasia, necrotising
enterocolitis.
5. IUGR (as defined by the trialists).
Types of interventions 6. Fetal distress (as defined by the study authors).
Doppler ultrasound of the utero-placental circulation (uterine, 7. Neonatal resuscitation required (as defined by trialists).
arcuate, radial and spiral arteries) in pregnancies at low and high 8. Infant requiring intubation/ventilation.
risk. We did not include studies that considered the combination 9. Infant respiratory distress syndrome.
of utero-placental Doppler and fetal or umbilical Doppler in this 10. Apgar score less than seven at five minutes.
review, but did include them in fetal and umbilical Doppler reviews 11. Neonatal admission to special care or intensive care unit, or
(Alfirevic 2010a; Alfirevic 2010b). both.
12. Preterm birth (birth before 37 completed weeks of
pregnancy):
Comparisons i) spontaneous preterm birth;
1. Doppler ultrasound of utero-placental vessels versus no ii) iatrogenic preterm birth.
Doppler ultrasound of utero-placental vessels (including 13. Caesarean section (elective and emergency).
comparisons of Doppler ultrasound of utero-placental vessels 14. Caesarean section - elective.

15. Caesarean section - emergency. Data collection and analysis
16. Serious maternal morbidity and mortality (composite
The methodology for data collection and analysis was based on the
outcome with death of a woman while pregnant or within 42
Cochrane Handbook of Systematic Reviews of Interventions (Higgins
days of termination of pregnancy).
2008).
17. Mother’s admission to special care or intensive care unit, or
both.
18. Gestational age at birth. Selection of studies
19. Infant birthweight.
Two review authors (TS, GG) independently assessed for inclusion
20. Length of infant hospital stay.
all potential studies we identified as a result of the search strategy.
21. Length of maternal hospital stay.
We resolved any disagreement through discussion or, if required,
* Perinatal death excluding chromosomal abnormalities, termina-
we consulted the third author (ZA).
tion of pregnancies, birth before fetal viability (as defined by tri-
alists) and fetal death before use of the intervention.
Data extraction and management
We designed a form to extract data. For eligible studies, two re-
view authors (TS, GG) extracted the data using the agreed form,
Search methods for identification of studies with additional help at times (Stephania Livio). We resolved dis-
crepancies 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).
Electronic searches When information regarding any of the above was unclear, we
attempted to contact authors of the original reports to provide
We contacted the Trials Search Co-ordinator to search the
further details.
Cochrane Pregnancy and Childbirth Group’s Trials Register (June
2010).
The Cochrane Pregnancy and Childbirth Group’s Trials Register Assessment of risk of bias in included studies
is maintained by the Trials Search Co-ordinator and contains trials
Two review authors (TS, GG) independently assessed risk of bias
identified from:
for each study using the criteria outlined in the Cochrane Handbook
1. quarterly searches of the Cochrane Central Register of
for Systematic Reviews of Interventions (Higgins 2008). We resolved
Controlled Trials (CENTRAL);
any disagreement by discussion or by involving the third author
2. weekly searches of MEDLINE;
(ZA).
3. handsearches of 30 journals and the proceedings of major
conferences;
4. weekly current awareness alerts for a further 44 journals (1) Sequence generation (checking for possible selection
plus monthly BioMed Central email alerts. bias)
Details of the search strategies for CENTRAL and MEDLINE,
We describe for each included study the method used to generate
the list of handsearched journals and conference proceedings, and
the allocation sequence in sufficient detail to allow an assessment
the list of journals reviewed via the current awareness service can
of whether it should produce comparable groups.
be found in the ‘Specialized Register’ section within the edito-
We assessed the method as:
rial information about the Cochrane Pregnancy and Childbirth
• adequate (any truly random process, e.g. random number
Group.
table; computer random-number generator);
Trials identified through the searching activities described above
• inadequate (any non-random process, e.g. odd or even date
are each assigned to a review topic (or topics). The Trials Search
of birth; hospital or clinic record number);
Co-ordinator searches the register for each review using the topic
• unclear.
list rather than keywords.
(2) Allocation concealment (checking for possible selection

bias)
Searching other resources
We describe for each included study the method used to conceal
We searched the reference lists at the end of papers for further the allocation sequence in sufficient detail and determine whether
studies. intervention allocation could have been foreseen in advance of, or
We did not apply any language restrictions. during recruitment, or changed after assignment.

We assessed the methods as: incompletely and so cannot be used; study fails to include results
• adequate (e.g. telephone or central randomisation; of a key outcome that would have been expected to have been
consecutively numbered sealed opaque envelopes); reported);
• inadequate (open random allocation; unsealed or non- • unclear.
opaque envelopes, alternation; date of birth);
• unclear.
(6) Other sources of bias
We describe for each included study any important concerns we
(3) Blinding (checking for possible performance bias) have about other possible sources of bias.
We describe for each included study the methods used, if any, to We assessed whether each study was free of other problems that
blind study participants and personnel from knowledge of which could put it at risk of bias:
intervention a participant received. We judged studies at low risk • yes;
of bias if they were blinded, or if we judged that the lack of blinding • no;
could not have affected the results. We assessed blinding separately • unclear.
for different outcomes or classes of outcomes.
We assessed the methods as:
(7) Overall risk of bias
• adequate, inadequate or unclear for participants;
• adequate, inadequate or unclear for personnel; We made explicit judgements about whether studies were at high
• adequate, inadequate or unclear for outcome assessors. risk of bias, according to the criteria given in the Cochrane Hand-
book for Systematic Reviews of Interventions (Higgins 2008). With
reference to (1) to (6) above, we assessed the likely magnitude and
(4) Incomplete outcome data (checking for possible attrition direction of the bias and whether we considered it is likely to im-
bias through withdrawals, dropouts, protocol deviations) pact on the findings. We explored the impact of the level of bias
We describe for each included study, and for each outcome or class through undertaking sensitivity analyses - see Sensitivity analysis.
of outcomes, the completeness of data including attrition and ex-
clusions from the analysis. We state whether attrition and exclu-
Measures of treatment effect
sions 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
Dichotomous data
were balanced across groups or were related to outcomes. Where
sufficient information was reported, or was supplied by the trial For dichotomous data, we present results as summary risk ratio
authors, we have re-included missing data in the analyses which with 95% confidence intervals.
we undertook. We assessed methods as:
• adequate;
Continuous data
• inadequate:
• unclear. For continuous data, we used the mean difference if outcomes are
measured in the same way between trials. We used the standardised
We were to discuss whether missing data greater than 20% might mean difference to combine trials that measure the same outcome,
impact on outcomes, acknowledging that with long-term follow but used different methods.
up, complete data are difficult to attain. However, none of the
included studies had greater than 20% missing data.
Unit of analysis issues
(5) Selective reporting bias

We describe for each included study how we investigated the pos- Cluster-randomised trials
sibility of selective outcome reporting bias and what we found. We would have included cluster-randomised trials in the analyses
We assessed the methods as: along with individually randomised trials, had we identified any.
• adequate (where it was clear that all of the study’s pre- We would have make adjustments using the methods described
specified outcomes and all expected outcomes of interest to the in the Cochrane Handbook for Systematic Reviews of Interventions
review have been reported); (Higgins 2008) using an estimate of the intracluster correlation co-
• inadequate (where not all the study’s pre-specified outcomes efficient (ICC) derived from the trial (if possible), or from another
have been reported; one or more reported primary outcomes source. If ICCs from other sources had been used, we would have
were not pre-specified; outcomes of interest were reported reported this and conducted sensitivity analyses to investigate the

effect of variation in the ICC. If we had identified both cluster- Data synthesis
randomised trials and individually-randomised trials, we would We carried out statistical analysis using the Review Manager soft-
have planned to synthesise the relevant information. We would ware (RevMan 2008). We used fixed-effect meta-analysis for com-
have considered it reasonable to combine the results from both if bining data where it was reasonable to assume that studies were
there was little heterogeneity between the study designs and the estimating the same underlying treatment effect: i.e. where trials
interaction between the effect of intervention and the choice of were examining the same intervention, and the trials’ populations
randomisation unit were considered to be unlikely. and methods were judged sufficiently similar. If there was clinical
We would also have acknowledged any heterogeneity in the ran- heterogeneity sufficient to expect that the underlying treatment ef-
domisation unit and perform a separate meta-analysis. fects differ between trials, or if substantial statistical heterogeneity
was detected, we would have used random-effects analysis to pro-
duce an overall summary, if this was considered clinically mean-
Cross-over trials ingful. If an average treatment effect across trials was not clinically
We considered cross-over designs inappropriate for this research meaningful, we would not have combined heterogeneous trials. If
question. 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,
Dealing with missing data and the estimates of T² and I² (Higgins 2009).
For included studies, we noted levels of attrition. We would have
explored the impact of including studies with high levels of miss-
Subgroup analysis and investigation of heterogeneity
ing data in the overall assessment of treatment effect by using sen-
sitivity analysis. We had planned to carry out the following subgroup analyses on
For all outcomes, we carried out analyses, as far as possible, on an all outcomes:
intention-to-treat basis, i.e. we attempted to include all partici- 1. measurements in high-risk population, low-risk population
pants randomised to each group in the analyses. The denominator and unselected population;
for each outcome in each trial is the number randomised minus 2. in singleton and twin pregnancies.
any participants whose outcomes were known to be missing. We However, there were insufficient data to perform any subgroup
would have excluded data on outcomes where there was greater analyses. We had also planned to pull together the three subgroups
than 20% missing data on short term outcomes had we encoun- for the overall estimation.
tered such data. 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-analy-
Assessment of heterogeneity ses, we would have assessed differences between subgroups by in-
We assessed statistical heterogeneity in each meta-analysis using spection of the subgroups’ confidence intervals; non-overlapping
the T² (tau-squared), I² and Chi² statistics. We regarded hetero- confidence intervals indicate a statistically significant difference in
geneity as substantial if T² was greater than zero and either I² was treatment effect between the subgroups.
greater than 30% or there was a low P-value (less than 0.10) in the
Chi² test for heterogeneity. Where we found heterogeneity and Sensitivity analysis
random-effects was used, we have reported the average risk ratio,
We would have performed sensitivity analysis on the primary out-
or average mean difference or average standard mean difference.
comes based on trial quality, separating high-quality trials from
trials of lower quality. ’High quality’ would, for the purposes of
Assessment of reporting biases this sensitivity analysis, have been defined as a trial having ade-
quate sequence generation and allocation concealment.
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 vi-
sually, and use formal tests for funnel plot asymmetry. For contin-
RESULTS
uous 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
Description of studies
would have performed exploratory analyses to investigate it. We See: Characteristics of included studies; Characteristics of excluded
would seek statistical help if necessary. studies; Characteristics of studies awaiting classification.

Results of the search Included studies compared uterine artery Doppler assessments in
The search was designed to identify all randomised controlled trials the experimental group with no uterine artery Doppler performed
on assessing the effectiveness of Doppler ultrasound, whether us- in the control groups (Goffinet 2001; Subtil 2003). In both stud-
ing fetal-umbilical or utero-placental (maternal) vessels. We iden- ies, low-dose aspirin was administrated in cases of abnormal uter-
tified 58 publications from 34 studies, of which we have included ine artery Doppler findings (Goffinet 2001; Subtil 2003).
two in this review, involving data on 4993 women and 5009 Both studies were of assessments of women in the second trimester,
neonates (Goffinet 2001; Subtil 2003). around time for fetal anomaly scan, and both included women at
We have excluded 30 studies, mainly because they assessed both fe- low risk for hypertensive disorders (Goffinet 2001; Subtil 2003).
tal and umbilical vessels. For further details of trial characteristics, One of the studies involved a mixture of singleton and twin preg-
please refer to the tables of Characteristics of included studies and nancies (Subtil 2003), while the other did not state specifically if
Characteristics of excluded studies. Two studies are awaiting classi- it included multiple pregnancies, although reported numbers sug-
fication as we are trying to locate the authors but they both appear gest only singleton pregnancies were included (Goffinet 2001).
to remain unpublished (Ellwood 1997; Snaith 2006). The large
number of excluded studies reflects the fact that the search was
Excluded studies
designed for all Doppler ultrasound studies, including both utero-
placental vessels and fetal-umbilical vessels. Most of the studies We excluded 30 studies, mostly because they assessed umbilical
identified focused on fetal-umbilical vessels and are included by artery Doppler ultrasound. See Characteristics of excluded studies.
two other Doppler ultrasound reviews (Alfirevic 2010a; Alfirevic
2010b).
Risk of bias in included studies
The quality of the three included studies was reasonable, although
Included studies blinding was not possible (Figure 1).
Figure 1. Methodological quality summary: review authors’ judgements about each methodological quality
item for each included study.

Allocation
We found no studies assessing uterine artery Doppler ultrasound
Both studies had adequate sequence generation and concealment in the first trimester.
allocation (Goffinet 2001; Subtil 2003).
Blinding 2. Uterine artery Doppler ultrasound versus no

Blinding women and/or staff in these trials was not generally fea- Doppler ultrasound, 2nd trimester (two studies, 4993
sible. Some outcomes like induction of labour and caesarean sec- women)
tion may be influenced by the knowledge of Doppler results, but We identified two studies assessing uterine artery Doppler ultra-
it may be possible to avoid bias in neonatal assessment. Unfortu- sound in the second trimester in women at low risk for hyperten-
nately, the information on the attempts to protect against biased sive disorders (Goffinet 2001; Subtil 2003). Both were full pub-
assessment was not available. lications (Goffinet 2001; Subtil 2003). Overall the quality of the
included studies was good for the main criteria of randomisa-
Incomplete outcome data tion, allocation concealment and low percentage of missing data
(Goffinet 2001; Subtil 2003), see Figure 1.
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 Primary outcomes
164. As this was not a block randomisation, we cannot be sure
It is important to emphasise that this review remains underpow-
these are randomised groups being compared so we are awaiting
ered to detect clinically important differences in serious maternal
the full study to be reported before including any data.
and neonatal morbidity.
Selective reporting
We assessed both included studies as unclear because we did not Any perinatal death after randomisation
assess the trial protocols.
The difference in perinatal mortality between two groups was not
statistically significant (average risk ratio (RR) 1.61, 95% confi-
Other potential sources of bias dence interval (CI) 0.48 to 5.39, two studies, 5009 babies, Analysis
One study appeared free of other biases (Subtil 2003), whilst for 2.1). The heterogeneity was high (T² = 0.55, Chi² P = 0.06, I²
the other this was unclear (Goffinet 2001). = 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.
Sensitivity analyses Subtil 2003 reported significantly fewer deaths in the control
For sensitivity analyses by quality of studies, we have used both ad- group (RR 3.14, 95% CI 1.10 to 8.98). This difference was con-
equate labelled sequence generation and adequate allocation con- tributed to by 17 abortions or medically indicated terminations of
cealment as essential criteria for high quality. Two of three stud- pregnancy in the 1253 women in the Doppler group (1.4%) com-
ies met these criteria (Goffinet 2001; Subtil 2003), see Figure 1. pared with three out of 617 in the control group (0.5%). In addi-
However, we feel there are insufficient data to perform a sensitivity tion, 78 of the 1253 women randomised to Doppler group (6.2%)
analysis by quality. did not receive their allocated treatment. The reason was termina-
tion of pregnancies for medical or social reasons in 15 women and
perinatal deaths in two babies, but the reasons for the remainder
Effects of interventions
of the women not receiving the Doppler ultrasound were not doc-
umented. The analysis for ’Any potentially preventable perinatal
death after randomisation’ which excluded all terminations and
1. Uterine artery Doppler ultrasound versus no
perinatal deaths for chromosomal abnormalities is more clinically
Doppler ultrasound, 1st trimester (no studies)
relevant and showed no detectable difference (see below).
Hypertensive disorders Sensitivity analysis
There was no difference identified in maternal hypertensive dis- Since we assessed both studies as adequate for sequence generation
orders between two groups (RR 1.08, 95% CI 0.87 to 1.33, two and allocation concealment (Goffinet 2001; Subtil 2003), we did
studies, 4987 women, Analysis 2.2). not undertake sensitivity analysis by quality.
Secondary outcomes DISCUSSION

We found no significant difference in the pooled estimate of the in- Increasing interest in maternal Doppler in first and second
tervention effect for the range of secondary outcomes with low het- trimester led us to undertake this review which completes a trio
erogeneity where a fixed-effect meta-analysis was used. Most pre- of reviews on Doppler ultrasound in pregnancy. The other two
specified secondary outcomes had high heterogeneity and there- reviews focused on the use of fetal-umbilical Doppler ultrasound
fore an intervention effect estimate across studies was calculated in high risk (Alfirevic 2010a) and normal pregnancies (Alfirevic
using random-effects. 2010a).
There was no significant difference in stillbirths (average RR 1.44, Despite wide use of uterine artery Doppler ultrasound in clinical
95% CI 0.38 to 5.49, two studies, 5003 babies, random-effects practice, we identified just two randomised studies assessing this
T² = 0.70, Chi² P = 0.04, I² = 75%, Analysis 2.3), or for neonatal intervention in the second trimester of pregnancy involving 4993
deaths (RR 2.39, 95% CI 0.39 to 14.83, two studies, 5009 babies, women at low risk of hypertensive disorders (Goffinet 2001; Subtil
Analysis 2.4). Similarly for ’Any potentially preventable perinatal 2003) and found no difference in any perinatal or maternal out-
death after randomisation’ (average RR 1.29, 95% CI 0.21 to 7.94, comes. Considering that both included studies involved women at
two studies, 5009 babies, random-effects T² 1.09, Chi² P = 0.11, I² low risk for hypertensive disorders, this could possibly explain the
= 60%, Analysis 2.5). These data should be interpreted cautiously lack of benefit identified for uterine artery Doppler application
because the numbers are small and heterogeneity is high. as incidence of adverse outcomes was low (any potentially pre-
The data for neonatal admission to special care baby unit (SCBU) ventable perinatal death 0.4%, hypertensive disorders 7%, IUGR
or neonatal intensive care unit (NICU) (RR 1.12, 95% CI 0.92 11%).
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, In both studies (Goffinet 2001; Subtil 2003), the finding of patho-
4982 women, random-effects T² = 0.09, Chi² P = 0.15, I² = 51%, logical uterine artery Doppler was followed by low-dose aspirin
Analysis 2.15) are consistent with the overall picture showing no administration. When interpreting these data, it is important to
significant difference in two groups. The meta-analysis also failed highlight the presence of heterogeneity and small number of par-
to identify any difference in IUGR (average RR 0.98, 95% CI ticipants that makes our review underpowered rare events such as
0.64 to 1.50, two studies, 5006 babies, random-effects T² = 0.08, perinatal mortality and severe maternal outcomes.
Chi² P = 0.02, I² = 82%, Analysis 2.7), although there was high Suprisingly, lower perinatal mortality was observed in the con-
heterogeneity, so it is also possible that there are different effects trol group in one study (Subtil 2003: risk ratio 3.14, 95% confi-
in the different studies, for unknown reasons. dence interval 1.10 to 8.98, Analysis 2.1). This could be possibly
Only one study assessed neonatal resuscitation (RR 0.94, 95% CI explained by a higher percentage of women with termination of
0.75 to 1.19, 3133 babies, Analysis 2.9), Apgar score less than pregnancy or perinatal death that occurred in the Doppler group
seven at five minutes (RR 1.08, 95% CI 0.48 to 2.45, 3133 babies) by chance before the Doppler ultrasound was carried out.
(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.
Summary of main results
None of the studies assessed the following outcomes: ’Serious
neonatal morbidity’, ’Fetal distress’, ’Infant requiring intubation/ We found no differences in any of the perinatal and maternal
ventilation’, ’Infant respiratory distress syndrome’, ’Spontaneous outcomes when comparing uterine artery Doppler ultrasound in
preterm birth’, ’Serious maternal morbidity’ and ’Maternal admis- the second trimester in women at low risk for hypertensive disor-
sion to special care’. ders versus controls. There were no studies of women in the first
trimester.
Non-prespecified outcomes Overall completeness and applicability of

We did not include any non-prespecified outcomes.
evidence

There were only two studies involving 4993 women, and clearly Implications for practice
the meta-analysis remains underpowered to show clinically im-
Data in this meta-analysis failed to show that the use of uterine
portant differences in primary outcomes. The identification of an
artery Doppler in second trimester in low-risk population for hy-
abnormal results also needs an effective intervention before the
pertensive disorders provides benefit for the baby or mother.
screening test can be said to be helpful.
Uterine artery Doppler ultrasound is widely used in high-risk preg-
nancy and progressively its use is spreading into the first trimester,
although there are no randomised studies to show clear benefit in
Quality of the evidence this population of women. Futher research is needed to prove the
The studies were of reasonable quality, but involved insufficient appropriateness of this clinical practice application.
numbers of women overall to assess the rare outcomes of perinatal
death and morbidity. Implications for research
As previously highlighted, larger studies are needed with enough
power to show clearly the presence or absence of benefit when
Potential biases in the review process using uterine artery Doppler ultrasound in second trimester in
low-risk women for hypertensive disorders. Moreover, randomised
We attempted to minimise bias in a number of ways; two review
controlled trials of uterine artery Doppler in the first and second
authors assessed eligibility for inclusion, carried out data extraction
trimester, in combination with woman’s history and/or biochemi-
and assessed risk of bias. Each worked independently. Nevertheless,
cal serum markers, are needed to evaluate the benefit of combined
the process of assessing risk of bias, for example, is not an exact models.
science and includes many personal judgements.
Agreements and disagreements with other ACKNOWLEDGEMENTS

studies or reviews
We would also like to thank Stefania Livio, who helped with some
Findings from this meta-analysis are not in disagreement with of the data extractions, and Eugenie Ong, who translated the de
other non-randomised studies that examined the role of uterine Rochambeau 1992 study.
arteries in low-risk population in second trimester of pregnancy.
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
Group’s international panel of consumers and the Group’s Statis-
AUTHORS’ CONCLUSIONS tical Adviser.
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∗
Indicates the major publication for the study

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 permu-
tations
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

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? No Not possible to blind.

All outcomes
Incomplete outcome data addressed? Yes Loss of participants to follow up at each

All outcomes 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 randomisa-
tion:
• “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.

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 second-
trimester 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 gesta-
tional 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 gen-
erated by the manufacturer of the treatment

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 ran-
domisation 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 con-
nection to an always available server.... Af-
ter verifying the inclusion criteria and the
patient’s consent, the server provided ei-
ther a treatment box number or the word
“Doppler” to the physician investigator. At
the end of prenatal consultation the physi-
cian 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? No It was not possible to blind participants and

All outcomes clinicians with regard to the use of Doppler
US or not (and the outcome assessor would
often be the clinician), although partici-
pants and clinicians were blind to the use
of aspirin or placebo in women with abnor-
mal Doppler US results
Incomplete outcome data addressed? Yes Loss of participants to follow up at each

All outcomes 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 randomisa-
tion:
• 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%)

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.

(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 ultra-
sound 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-

(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 quasi-
RCT; 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

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

DATA AND ANALYSES
Comparison 1. Uterine artery Doppler ultrasound versus no Doppler ultrasound, 1st trimester
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Any perinatal death after 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
randomisation
1.1 Women at increased risk 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
1.2 Women at low risk of 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
complications
1.3 Unselected population of 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
women
2 Hypertensive disorders 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
3 Stillbirth 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
4 Neonatal death 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
5 Any potentially preventable 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
perinatal death after
randomisation
of complications
complications
women
6 Serious neonatal morbidity - 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
composite
of complications
complications
women
7 Intrauterine growth restriction 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
8 Fetal distress 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
9 Neonatal resuscitation 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
10 Infant requiring intubation/ 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
ventilation
of complications
complications
women
11 Infant respiratory distress 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
syndrome
of complications
complications
women
12 Apgar score < 7 at 5 min 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
13 Neonatal admission to SCBU 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
or NICU

of complications
complications
women
14 Spontaneous preterm birth (< 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
37 weeks)
of complications
complications
women
15 Iatrogenic preterm birth (< 37 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
weeks)
of complications
complications
women
16 Caesarean section (both elective 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
and emergency)
of complications
complications
women
17 Elective caesarean section 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
18 Emergency caesarean section 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
19 Serious maternal morbidity and 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
mortality
of complications
complications

women
20 Mothers admission to special 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
care or intensive care unit
of complications
complications
women
21 Gestational age at birth 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
21.1 Women at increased risk 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
of complications
21.2 Women at low risk of 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
complications
21.3 Unselected population of 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
women
22 Infant birthweight 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
of complications
complications
women
23 Length of infant hospital stay 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
of complications
complications
women
24 Length of maternal hospital 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
stay
of complications
complications
women
Comparison 2. Uterine artery Doppler ultrasound versus no Doppler ultrasound, 2nd trimester
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Any perinatal death after 2 5009 Risk Ratio (M-H, Random, 95% CI) 1.61 [0.48, 5.39]
randomisation
1.1 Women at increased risk 0 0 Risk Ratio (M-H, Random, 95% CI) Not estimable
of complications
1.2 Women at low risk of 2 5009 Risk Ratio (M-H, Random, 95% CI) 1.61 [0.48, 5.39]
complications
1.3 Unselected population of 0 0 Risk Ratio (M-H, Random, 95% CI) Not estimable
women
2 Hypertensive disorders 2 4987 Risk Ratio (M-H, Fixed, 95% CI) 1.08 [0.87, 1.33]
of complications
2.2 Women at low risk of 2 4987 Risk Ratio (M-H, Fixed, 95% CI) 1.08 [0.87, 1.33]
complications
women
3 Stillbirth 2 5003 Risk Ratio (M-H, Random, 95% CI) 1.44 [0.38, 5.49]
of complications
complications
women
4 Neonatal death 2 5009 Risk Ratio (M-H, Fixed, 95% CI) 2.39 [0.39, 14.83]
of complications
complications
women
5 Any potentially preventable 2 5009 Risk Ratio (M-H, Random, 95% CI) 1.29 [0.21, 7.94]
perinatal death after
randomisation
of complications
complications
women
6 Serious neonatal morbidity - 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
composite
of complications
complications
women
7 Intrauterine growth restriction 2 5006 Odds Ratio (M-H, Random, 95% CI) 0.98 [0.64, 1.50]
7.1 Women at increased risk 0 0 Odds Ratio (M-H, Random, 95% CI) Not estimable
of complications
7.2 Women at low risk of 2 5006 Odds Ratio (M-H, Random, 95% CI) 0.98 [0.64, 1.50]
complications
7.3 Unselected population of 0 0 Odds Ratio (M-H, Random, 95% CI) Not estimable
women

8 Fetal distress 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
of complications
complications
women
9 Neonatal resuscitation 1 3133 Risk Ratio (M-H, Fixed, 95% CI) 0.94 [0.75, 1.19]
of complications
complications
women
10 Infant requiring intubation/ 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
ventilation
of complications
complications
women
11 Infant respiratory distress 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
syndrome
of complications
complications
women
12 Apgar score < 7 at 5 min 1 3133 Risk Ratio (M-H, Fixed, 95% CI) 1.08 [0.48, 2.45]
of complications
complications
women
13 Neonatal admission to SCBU 2 5001 Risk Ratio (M-H, Fixed, 95% CI) 1.12 [0.92, 1.37]
or NICU
of complications
complications
women
14 Spontaneous preterm birth (< 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
37 weeks)
of complications

complications
women
15 Iatrogenic preterm birth (< 37 2 4982 Risk Ratio (M-H, Random, 95% CI) 0.92 [0.51, 1.65]
weeks)
of complications
complications
women
16 Caesarean section (both elective 1 3133 Risk Ratio (M-H, Fixed, 95% CI) 1.09 [0.91, 1.29]
and emergency)
of complications
complications
women
17 Elective caesarean section 1 3133 Risk Ratio (M-H, Fixed, 95% CI) 1.05 [0.82, 1.34]
of complications
complications
women
18 Emergency caesarean section 1 3133 Risk Ratio (M-H, Fixed, 95% CI) 1.13 [0.87, 1.46]
of complications
complications
women
19 Serious maternal morbidity and 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
mortality
of complications
complications
women
20 Mothers admission to special 0 0 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
care or intensive care unit
of complications
complications
women
21 Gestational age at birth 1 3133 Mean Difference (IV, Fixed, 95% CI) -0.10 [-0.24, 0.04]
of complications
21.2 Women at low risk of 1 3133 Mean Difference (IV, Fixed, 95% CI) -0.10 [-0.24, 0.04]
complications
women
22 Infant birthweight 1 3133 Mean Difference (IV, Fixed, 95% CI) -34.0 [-68.63, 0.63]
of complications
22.2 Women at low risk of 1 3133 Mean Difference (IV, Fixed, 95% CI) -34.0 [-68.63, 0.63]
complications
women
23 Length of infant hospital stay 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
of complications
complications
women
24 Length of maternal hospital 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable
stay
of complications
complications
women

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 Risk Ratio Weight Risk Ratio

M- M-
H,Random,95% H,Random,95%
n/N n/N CI CI
1 Women at increased risk of complications
Subtotal (95% CI) 0 0 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 ]
Subtotal (95% CI) 2821 2188 100.0 % 1.61 [ 0.48, 5.39 ]

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) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 2821 2188 100.0 % 1.61 [ 0.48, 5.39 ]
0.01 0.1 1 10 100

Favours Doppler Favours no Doppler

trimester, Outcome 2 Hypertensive disorders.
Outcome: 2 Hypertensive disorders

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 83/1572 81/1561 51.2 % 1.02 [ 0.76, 1.37 ]
Subtil 2003 133/1238 58/616 48.8 % 1.14 [ 0.85, 1.53 ]
Subtotal (95% CI) 2810 2177 100.0 % 1.08 [ 0.87, 1.33 ]

Heterogeneity: Chi2 = 0.29, df = 1 (P = 0.59); I2 =0.0%
Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 2810 2177 100.0 % 1.08 [ 0.87, 1.33 ]
0.5 0.7 1 1.5 2


trimester, Outcome 3 Stillbirth.
Outcome: 3 Stillbirth

M- M-
n/N n/N CI CI

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
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 ]
Subtotal (95% CI) 2825 2178 100.0 % 1.44 [ 0.38, 5.49 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 2825 2178 100.0 % 1.44 [ 0.38, 5.49 ]
0.05 0.2 1 5 20

trimester, Outcome 4 Neonatal death.
Outcome: 4 Neonatal death


Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
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 ]
Subtotal (95% CI) 2821 2188 100.0 % 2.39 [ 0.39, 14.83 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 2821 2188 100.0 % 2.39 [ 0.39, 14.83 ]
0.01 0.1 1 10 100


trimester, Outcome 5 Any potentially preventable perinatal death after randomisation.
Outcome: 5 Any potentially preventable perinatal death after randomisation

M- M-
n/N n/N CI CI

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
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 ]
Subtotal (95% CI) 2821 2188 100.0 % 1.29 [ 0.21, 7.94 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 2821 2188 100.0 % 1.29 [ 0.21, 7.94 ]
0.01 0.1 1 10 100


trimester, Outcome 7 Intrauterine growth restriction.
Outcome: 7 Intrauterine growth restriction
Study or subgroup Doppler US No Doppler US Odds Ratio Weight Odds Ratio

M- M-
n/N n/N CI CI

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
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 ]
Subtotal (95% CI) 2818 2188 100.0 % 0.98 [ 0.64, 1.50 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 2818 2188 100.0 % 0.98 [ 0.64, 1.50 ]
0.01 0.1 1 10 100


trimester, Outcome 9 Neonatal resuscitation.
Outcome: 9 Neonatal resuscitation


Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 127/1572 134/1561 100.0 % 0.94 [ 0.75, 1.19 ]
Subtotal (95% CI) 1572 1561 100.0 % 0.94 [ 0.75, 1.19 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 1572 1561 100.0 % 0.94 [ 0.75, 1.19 ]
Test for subgroup differences: Not applicable
0.01 0.1 1 10 100


trimester, Outcome 12 Apgar score < 7 at 5 min.
Outcome: 12 Apgar score < 7 at 5 min


Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 12/1572 11/1561 100.0 % 1.08 [ 0.48, 2.45 ]
Subtotal (95% CI) 1572 1561 100.0 % 1.08 [ 0.48, 2.45 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 1572 1561 100.0 % 1.08 [ 0.48, 2.45 ]
0.01 0.1 1 10 100


trimester, Outcome 13 Neonatal admission to SCBU or NICU.
Outcome: 13 Neonatal admission to SCBU or NICU


Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 142/1572 121/1561 74.0 % 1.17 [ 0.92, 1.47 ]
Subtil 2003 63/1242 32/626 26.0 % 0.99 [ 0.66, 1.50 ]
Subtotal (95% CI) 2814 2187 100.0 % 1.12 [ 0.92, 1.37 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 2814 2187 100.0 % 1.12 [ 0.92, 1.37 ]
0.01 0.1 1 10 100


trimester, Outcome 15 Iatrogenic preterm birth (< 37 weeks).
Outcome: 15 Iatrogenic preterm birth (< 37 weeks)

M- M-
n/N n/N CI CI

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
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 ]
Subtotal (95% CI) 2809 2173 100.0 % 0.92 [ 0.51, 1.65 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 2809 2173 100.0 % 0.92 [ 0.51, 1.65 ]
0.01 0.1 1 10 100


trimester, Outcome 16 Caesarean section (both elective and emergency).
Outcome: 16 Caesarean section (both elective and emergency)


Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 232/1572 212/1561 100.0 % 1.09 [ 0.91, 1.29 ]
Subtotal (95% CI) 1572 1561 100.0 % 1.09 [ 0.91, 1.29 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 1572 1561 100.0 % 1.09 [ 0.91, 1.29 ]
0.01 0.1 1 10 100


trimester, Outcome 17 Elective caesarean section.
Outcome: 17 Elective caesarean section


Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 117/1572 111/1561 100.0 % 1.05 [ 0.82, 1.34 ]
Subtotal (95% CI) 1572 1561 100.0 % 1.05 [ 0.82, 1.34 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 1572 1561 100.0 % 1.05 [ 0.82, 1.34 ]
0.01 0.1 1 10 100


trimester, Outcome 18 Emergency caesarean section.
Outcome: 18 Emergency caesarean section


Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 115/1572 101/1561 100.0 % 1.13 [ 0.87, 1.46 ]
Subtotal (95% CI) 1572 1561 100.0 % 1.13 [ 0.87, 1.46 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 1572 1561 100.0 % 1.13 [ 0.87, 1.46 ]
0.01 0.1 1 10 100


trimester, Outcome 21 Gestational age at birth.
Outcome: 21 Gestational age at birth
Mean Mean
Study or subgroup Doppler US No Doppler US Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 1572 39 (2) 1561 39.1 (2) 100.0 % -0.10 [ -0.24, 0.04 ]
Subtotal (95% CI) 1572 1561 100.0 % -0.10 [ -0.24, 0.04 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 1572 1561 100.0 % -0.10 [ -0.24, 0.04 ]
-100 -50 0 50 100

Favours no Doppler Favours Doppler

trimester, Outcome 22 Infant birthweight.
Outcome: 22 Infant birthweight
Mean Mean
Study or subgroup Doppler US No Doppler US Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Goffinet 2001 1572 3282 (503) 1561 3316 (486) 100.0 % -34.00 [ -68.63, 0.63 ]
Subtotal (95% CI) 1572 1561 100.0 % -34.00 [ -68.63, 0.63 ]

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Total (95% CI) 1572 1561 100.0 % -34.00 [ -68.63, 0.63 ]
-100 -50 0 50 100

Favours no Doppler Favours Doppler
HISTORY
Protocol first published: Issue 2, 2010
Review first published: Issue 9, 2010

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


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Utero-placental Doppler ultrasound for improving pregnancy

Stampalija T, Gyte GML, Alfirevic Z

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

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

Utero-placental Doppler ultrasound for improving pregnancy

Tamara Stampalija1 , Gillian ML Gyte2 , Zarko Alfirevic3

Editorial group: Cochrane Pregnancy and Childbirth Group.

Data collection and analysis

We identified no difference in short-term maternal and fetal clinical outcomes.

PLAIN LANGUAGE SUMMARY

BACKGROUND is replacement of the muscular and elastic arterial layer by collagen

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 3

Types of studies Types of outcome measures

All randomised trials and quasi-randomised studies comparing

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 4

(2) Allocation concealment (checking for possible selection

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 5

(5) Selective reporting bias

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 6

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 7

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 8

Blinding 2. Uterine artery Doppler ultrasound versus no

Secondary outcomes DISCUSSION

Non-prespecified outcomes Overall completeness and applicability of

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 10

Agreements and disagreements with other ACKNOWLEDGEMENTS

References to studies included in this review Obstetrics & Gynaecology 2003;110(5):485–91.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 14

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 15

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 16

Characteristics of included studies [ordered by study ID]

Participants Inclusion criteria:

Interventions Experimental intervention: uterine artery Doppler US

Item Authors’ judgement Description

Adequate sequence generation? Yes • “The randomisation was stratified

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 17

established using tables of order four

Allocation concealment? Yes • Randomisation procedure using

Blinding? No Not possible to blind.

Incomplete outcome data addressed? Yes Loss of participants to follow up at each

Free of other bias? Unclear 2 centres stopped inclusions a few month

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 18

Participants Inclusion criteria:

Interventions Experimental intervention: uterine artery Doppler US

Item Authors’ judgement Description

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 19

boxes before the study began. Treatment

Allocation concealment? Yes “...each patient was randomly allocated to a

Blinding? No It was not possible to blind participants and

Incomplete outcome data addressed? Yes Loss of participants to follow up at each

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 20

women in Doppler group.

AFI: amniotic fluid index

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.

de Rochambeau 1992 Study assessing umbilical artery Doppler ultrasound.

Utero-placental Doppler ultrasound for improving pregnancy outcome (Review) 21

Doppler 1997 Study assessing umbilical artery Doppler ultrasound.

Haley 1997 Study assessing umbilical artery Doppler ultrasound.