Postgraduate Training Course in Reproductive
Doppler ultrasound in high risk pregnancies
(Protocol for a Cochrane Systematic Review)
Dr. Cristiane Barbieri, MD
Department of Obstetrics and Gynaecology of the Center for Integral Attention
to Women’s Health (CAISM)
State University of Campinas (UNICAMP), Brazil
ultrasound has been used in almost every medical discipline to study
blood flow in diseases where an alteration of this dynamic system is anticipated.
Until this development the only way to study circulation was the invasive
technique of angiography. With the availability of this technique, it has
been possible to study the circulation patterns and their pathologies non-invasively.
The first Doppler ultrasound report using continuous wave assessment of
umbilical artery flow was published in 1977 (Fitzgerald 1977). With the
same systems, in 1983, Campbell published the assessment of the utero-placental
circulation and that high resistance waveforms were obtained in pre-eclampsia
(Campbell 1983) (Berkowitz 1988). Subsequently these studies were done with
colour Doppler and in many centers this has become an important screening
technique to predict women at risk of pre-eclampsia. In the colour
Doppler imaging, a real-time, two-dimensional flow imaging technique utilizes
an auto-correlation processor for the detection of a moving target. With
this method, color is assigned to flow direction. Customarily, flow towards
the Doppler transducer is displayed in red and flow away from it is shown
in blue. The structures that do not move are presented in basic gray-scale
image. Color flow imaging facilitates the detection of small vessels and
slow blood-flow velocity. With the use of colour Doppler, in 1987,
it was possible to study the middle cerebral artery in fetuses and compare
to umbilical artery pulsatility index (PI) ratio to demonstrate centralization
of the fetal circulation (Wladimiroff 1987). Centralization indicates a
high resistance in the feto-placental circulation and the study of the middle
cerebral artery shows inadequate cerebral perfusion.
The Doppler studies in Obstetrics and gynecology made a significant advance
following describing waveforms in the ductus venosus, which is now recognized
as a key examination to predict right heart failure in the hypoxic fetus
and an important indicator of imminent fetal demise (Kiserud 1991). Ductus
venosus leads directly into the vena cava; allows some blood rich in oxygen
and nutrients to be pumped out of the body without passing through the capillary
beds in the kidney. The presence of reversed flow in the ductus venosus
is an ominous sign. The relationship between abnormal uterine artery Doppler
velocimetry and pre-eclampsia, intra-uterine growth retardation and adverse
pregnancy outcome is well established (Aquilina 1996). Maternal hypertensive
disorders are often associated with inadequate blood supply through the
Pre-eclampsia occurs more commonly during first pregnancies, with twins
or triplets, in very young or older women, and when a woman has had pre-eclampsia
in previous pregnancies. In general, about 5-10 % of women get this condition
during their first pregnancy, while about 7% of women who have previously
had children develop pre- eclampsia with subsequent pregnancies (WHO 1988).
Doppler measurements can be obtained from the umbilical artery (UA), middle
cerebral artery (MCA), ductus venosus (DV) and uterine arteries. The pulsatility
index (PI) and resistance index (RI) are used for the arteries and the peak
velocity index (PVI) is used for the veins. Abnormal umbilical artery
Doppler flow velocimetry is defined as a pulsatility index (PI) >2 standard
deviations (SD) above the mean for gestational age and / or absence or reversal
of end-diastolic flow. Umbilical artery Doppler reflects downstream placental
vascular resistance, correlated with intrauterine growth restriction and
the multisystem effects of placental deficiency. Abnormalities are progressive,
with reduction, loss and finally a reversal of diastolic flow. When
blood flow in the umbilical arteries become abnormal, the differentiation
of fetus status requires Doppler information from systemic vessels, as middle
cerebral artery and ductus venosus. The middle cerebral artery is the vessel
of choice to assess the fetal cerebral circulation because it is easy to
identify. When the fetus is hypoxic, the cerebral arteries tend to become
dilated in order to preserve the blood flow to the brain. In the middle
cerebral artery, the systolic to diastolic (A/B) ratio will decrease
(due to an increase in diastolic flow) in the presence of chronic hypoxic
insult to the fetus. This increase in blood flow can be evidenced by Doppler
ultrasound of the middle cerebral artery. This effect has been called "brain
sparing effect" and is demonstrated by a lower value of the pulsatility
index. In fetuses with intrauterine growth restriction (IUGR) a pulsatility
index below the normal range indicates a greater risk of adverse perinatal
outcome. The brain sparing effect may be temporary, as reported during prolonged
hypoxemia in animal experiments, and the overstressed human fetus can also
lose the brain sparing effect. The disappearance of the brain sparing effect
is a critical event for the fetus, and appears to precede fetal death.
Doppler studies of uterine artery blood flow in the second trimester may
be useful in predicting pre-eclampsia and/or IUGR (Campbell 1986, 1993).
In normal pregnancy the systolic/diastolic ratio or RI values significantly
decrease with advancing gestation until 24 to 26 weeks. In the absence of
this physiologic decrease, a higher incidence of hypertensive diseases and/or
IUGR has been widely documented. Many indices have been devised but only
two are in regular clinical use. These are the resistance index (RI), also
known as the Pourcelot index and the pulsatility index (PI), also known
as the Gosling index. An advantage of these waveform indices is that they
consist of ratios of Doppler shift frequencies and thus are independent
of transmit frequency and Doppler angle. Doppler ultrasound of the umbilical
artery is more helpful than other tests of fetal wellbeing (Harman 2003),
namely cardiotocography and biophysical profile score in distinguishing
between the normal small fetus and the ‘sick’ small fetus (Soothil 1993).
Using cardiotocography for fetal surveillance, despite a low false-negative
rate, estimates of false-positive rates range from 50 to 80 % (Black 1997).
It is possible to use other methods for monitoring fetus in case of IUGR,
such as biophysical profile, which can complete the cardiotocography results
using the amniotic fluids levels and fetal movement during the exam (Manning
1980) (Vintzileos 1987).
At 22-24 weeks gestation if the fetus is measurably small by ultrasound,
several Doppler patterns may occur. The umbilical artery may still have
a normal pulsatility index (resistance index or S/D ratio), the middle cerebral
artery may have either a normal or abnormal pulsatility index. The second
possibility is when the umbilical artery has an abnormal pulsatility index
and the middle cerebral artery has either a normal or abnormal value of
pulsatility index. The other possibility occurs when both umbilical artery
and the middle cerebral artery have an abnormal value of pulsatility index.
In this case, there is a severe utero-placental insufficiency. The fetus
needs to be monitored very closed. Oligohydramnios may be present at any
stage of the above process. Ductus venosus reverse flow and umbilical veins
pulsation are present continuously. The fetus starts to lose the brain sparing
effect and the biophysical profile becomes abnormal (Gagnon 2003).
This sequence of events applies to a IUGR in cases of insufficiency placental
circulation and not to the fetuses who have other causes such as smoking,
abruption, and toxic drug exposure who may have a different pathology.
Since the first report of Doppler ultrasound evaluating high-risk pregnancies
in 1977, the fetal arterial system has been extensively studied to determine
if abnormal waveforms identify fetuses at increased risk of perinatal mortality.
Recent meta-analysis of randomized controlled trials suggests that incorporation
of umbilical artery Doppler waveform analysis into management protocols
for high risk pregnancies significantly decreases perinatal mortality (Neilson
1999). Other investigators suggested that the time period between identification
of an abnormal umbilical artery Doppler waveform and the development
of fetal distress and/or death varies widely – from days to weeks. Studies
show that there is a wide variability in the interval between detection
of umbilical absent or reverse end-diastolic flow velocities and occurrence
of heart rate decelerations (Kurkinen-Räty 1997). Therefore, the challenge
is to identify fetuses at greatest risk for adverse perinatal outcome when
abnormal umbilical artery waveforms are present.
The effects of Doppler ultrasound in high-risk pregnancies on obstetrical
care and fetal outcomes were systematically reviewed (Neilson 2003). The
use of Doppler in pregnancies complicated by hypertension or presumed impaired
fetal growth was associated with a trend in reduction of perinatal deaths.
The safety of Doppler ultrasound remains a concern. In particular the use
of pulsed Doppler involves the use of higher intensities compared to diagnostic
ultrasound, and may cause significant tissue heating and other thermal effects.
These thermal effects depend on the presence of a tissue/air interface and
may therefore not be clinically significant in obstetric ultrasound examinations
It is worth emphasizing that, screening is only worthwhile if an effective
preventive treatment is available. If we could identify the 'at-risk' fetus
using the Doppler ultrasound in order to apply clinical interventions, it
could result in reduced perinatal deaths and unnecessary obstetric interventions.
In many cases, the management consists of early delivery when the fetus
is mature or specific interventions for conditions such as pre-eclampsia.
To evaluate the benefits
and possible harms of the use of Doppler ultrasound screening in high risk
CRITERIA FOR CONSIDERING
STUDIES FOR THIS REVIEW
Types of studies
Randomized controlled trials of Doppler ultrasound as a clinical technique
to improve pregnancy outcome in high risk pregnancies.
Types of participants
Women with pregnancies deemed by the investigators to be at 'high-risk'.
The definitions of 'high-risk' are likely to include hypertensive disorders
of pregnancy, including pre-eclampsia and intrauterine growth restriction.
Women with multiple pregnancies are reviewed separately and will not be
included in this review.
Types of interventions
Doppler ultrasound of the umbilical artery and/or middle cerebral artery
and/or ductus venosus.
The study of the pulsatility index (PI), resistance index (RI) and systolic/diastolic
(S/D) ratio of the umbilical and uterine arteries, middle cerebral artery
All routine Doppler ultrasound versus no Doppler :
Umbilical artery Doppler versus no Doppler/ concealed Doppler examinations
Uterine artery Doppler versus no Doppler/ concealed Doppler examinations
Umbilical and uterine artery Doppler versus no Doppler/ concealed Doppler
Umbilical artery Doppler and ductus venosus Doppler versus no Doppler
/ concealed Doppler
Umbilical artery Doppler and middle cerebral artery versus no Doppler/
Doppler ultrasound and other monitoring methods versus other method
The study of the Doppler
ultrasound in high risk pregnancies can be done after the first trimester
once and/or more Doppler examinations during pregnancy.
Types of outcome measures
All outcome measures:
METHODS OF THE REVIEW
The review will use the
search strategy developed for the Cochrane Pregnancy and Childbirth Group
as a whole.
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