Umbilical Artery

Doppler in the
Assessment of Fetal
G ro w t h R e s t r i c t i o n
Dev Maulik, MD, PhD*, David Mundy, MD, Erica Heitmann, MD,
Devika Maulik, MD

KEYWORDS
 Umbilical artery Doppler  Fetal growth restriction
 Randomized trials  Evidence-based practice

Constrained fetal growth continues to be one of the major complications of pregnancy.

Affecting 5% to 10% of all gestations, fetal growth restriction (FGR) is associated with
significant increases in morbidity and mortality in the perinatal period and in infancy. It
is also apparent that FGR may initiate fetal epigenetic programming leading to the
subsequent development of a spectrum of cardiovascular and metabolic disorders
in adult life. FGR has varied etiology.1 Many aspects of this multifaceted problem still
remain unclear. However, meaningful advances have been made in recent years in
the antenatal monitoring of FGR based on the best available evidence of effectiveness.
Technological and clinical advances over the last 4 decades led to the innovation of
a variety of fetal surveillance tests, including the emergence of diagnostic Doppler
ultrasound for noninvasive assessment of umbilical and fetal circulations.2,3 Although
most of the currently used antepartum fetal monitoring tests, such as the nonstress
test (NST) and biophysical profile (BPP), have demonstrated significant diagnostic
efficacy, only the umbilical artery Doppler ultrasound has shown clinical effectiveness
in improving the perinatal outcome, especially in pregnancies complicated with FGR. In
this article, the authors appraise the use of UA Doppler for fetal surveillance in FGR,
specifically addressing its diagnostic efficacy and clinical effectiveness. In categorizing
the levels of evidence and recommendations, the authors have followed the guidelines
of the United States Preventive Services Task Force.4

FETAL PLACENTAL VASCULAR DEVELOPMENT IN FETAL GROWTH RESTRICTION

Fetal growth compromise is associated with abnormal vascular development of the

placenta. Fetal placental vascular development is characterized by vasculogenesis

Department of Obstetrics and Gynecology, University of Missouri Kansas City School of

Medicine, Kansas City, MO, USA
* Corresponding author.
E-mail address: maulikd@umkc.edu

Clin Perinatol 38 (2011) 65–82

doi:10.1016/j.clp.2010.12.004 perinatology.theclinics.com
0095-5108/11/$ – see front matter Ó 2011 Published by Elsevier Inc.
66 Maulik et al

followed by angiogenesis. During vasculogenesis, primitive capillary networks are

formed within the stroma of immature and mesenchymal villi between postconception
day 21 to approximately day 32, which is followed by mostly branching angiogenesis
until 24 weeks. Beyond 24 weeks, nonbranching angiogenesis dominates.5 As the
fetoplacental arterial system expands, there is concomitant fall in the flow impedance.
This action is mirrored in the progressive increase in the umbilical arterial end diastolic
flow and consequent decline in the arterial flow pulsatility with advancing gestation
(Fig. 1). It was shown experimentally by Maulik and colleagues6 that the arterial
Doppler indices reflect the state of the downstream flow impedance.
In pregnancies complicated with FGR and preeclampsia, there is a preponderance
of nonbranching angiogenesis,7 which results in substantial reductions in placental
vascularity and maternal-fetal exchange area. When the umbilical artery end diastolic
velocity is absent or reversed in FGR pregnancies, the gas exchanging villi are slender,
less abundant, and have poor capillary formation (Fig. 2).8 The resulting circulatory
dysfunction leads to chronic fetal deprivation and hypoxia, which may eventually
progress to acidosis and serious fetal compromise.

FETAL COMPENSATION AND DECOMPENSATION IN FETAL GROWTH RESTRICTION

Encountering chronic hypoxia, a growth restricted fetus mobilizes a spectrum of

compensatory responses that include preferential preservation of fetal growth over
placental growth, changes in the fetal movement patterns, and eventual deceleration
of the fetal growth rate. With continuing deprivation, compensation gives way to
decompensation. Fetal hemodynamic response involves flow redistribution favoring
perfusion of the vital organs (the brain, heart, and adrenals) at the expense of perfusion
of less critical tissues and organs, such as the muscle, viscera, and skin. Underlying
this phenomenon are the diverse changes in blood-flow impedance in fetal regional
circulations.
As fetoplacental arterial impedance increases, the end diastolic flow in the umbilical
artery declines and eventually disappears. As a response to hypoxia, fetal cerebral
vasodilation occurs and the middle cerebral artery Doppler indices decline. This
response in fetal cerebral circulation has been described as the “brain sparing effect”
although recent evidence suggests that this compensatory mechanism may not actu-
ally be neuroprotective in the long term.9
With progressive fetal deprivation and developing acidosis, the fetus stops moving,
umbilical artery end diastolic flow becomes reversed, and the fetal heart rate variability
disappears. Fetal cardiac function is compromised leading to an absence or reversal
of flow during atrial contractions in the ductus venosus and pulsations in the umbilical
vein. These are preterminal changes that ultimately lead to fetal demise in the absence
of any intervention. The order and severity of the previously mentioned changes are
modulated by other factors, such as the timing of onset, severity and progression of
FGR, and also any associated complications.
The sequence of compensation and decompensation is graphically depicted in
Fig. 3 and is discussed further later in this article.

PERINATAL OUTCOME IN FETAL GROWTH RESTRICTION

A growth-restricted fetus is at an increased risk of perinatal morbidity and mortality.10

The morbidities include prematurity, oligohydramnios, nonreassuring fetal heart rate
patterns with higher incidence of cesarean delivery, birth asphyxia, low Apgar score,
neonatal hypoglycemia, hypocalcemia, polycythemia, hyperbilirubinemia, hypo-
thermia, apnea, neurologic compromise, and infection.11 Perinatal death rate is also
 Umbilical Artery Doppler 67

Fig. 1. Gestational age effect on the umbilical arterial Doppler frequency shift waveforms.
Panels are organized from the top to the bottom according to advancing gestation. (A)
Waveforms at 16 weeks, (B) waveforms at 20 weeks, (C) waveforms at 24 weeks, (D) wave-
forms at 28 weeks, (E) waveforms at 32 weeks, (F) waveforms at 36 weeks. Note the progres-
sive increase in the end-diastolic velocity and the concomitant fall in the pulsatility as the
gestation advances. (From Maulik, D. Doppler ultrasound in obstetrics and Gynecology.
2nd edition. Springer: Germany; 2005; with permission.)
68 Maulik et al

Fig. 2. Typical peripheral villi of pregnancies complicated by positive end-diastolic umbilical

blood flow (A, B) and by absent or reverse end-diastolic umbilical blood flow (C, D). (B, D)
Immunostained sections. The oblique line across the villi refers to the position of the cross
section. (From Todros T, Sciarrone A, Piccoli E, et al. Umbilical Doppler waveforms and
placental villous angiogenesis in pregnancies complicated by fetal growth restriction.
Obstet Gynecol 1999;93:499–503; with permission.)

increased and is influenced by several factors, including the gestational age, severity
and timing of onset of growth restriction, and etiology. The lower the birth weight
centile for the gestational age, the higher the mortality. For example, Krammer and
associates12 noted that the fetal and neonatal death rate increased respectively
from 1.2% and 0.7% with mild growth restriction to 7.1% and 1.4% with severe
growth restriction. In most instances, there is no effective therapeutic intervention
for rectifying subnormal growth. The objective of fetal surveillance in FGR pregnancies
is to improve the outcome by determining the optimal time for intervention, balancing
between the risks of intrauterine death or injury and those of prematurity.

DOPPLER SONOGRAPHY OF THE UMBILICAL ARTERY

The umbilical artery can be interrogated using continuous, pulse Doppler or color
Doppler modes. Duplex Doppler ultrasound incorporating pulse spectral Doppler
with 2-dimensional gray scale or color Doppler imaging is the current standard for
umbilical artery Doppler sonography. A duplex Doppler interrogation of the umbilical
artery is depicted in Fig. 4.
There are many techniques of Doppler analysis. For clinical use, the main approach
has been analyzing the pulsatility of the Doppler waveform. The magnitude of the
waveform depends on the angle of insonation between the Doppler beam and the
vessel axis. A Doppler index is calculated as a ratio and is, therefore, virtually
independent of the angle of insonation. The indices are derived from the following
characteristics of the maximum frequency shift envelope (Fig. 5): the peak systolic
 Umbilical Artery Doppler 69

Fig. 3. Fetal response to chronic deprivation. The sequence of fetal response to chronic
intrauterine deprivation is depicted showing progression from compensation to decompen-
sation with fetal hypoxia deteriorating to asphyxia. Without timely intervention, the fetus
will sustain multisystem injury and will eventually die. Note that the chronology of events
may vary from patient to patient.

Fig. 4. Duplex Doppler sonography of the umbilical arterial flow. The upper panel shows
2-dimensional gray scale and color (gray scale in the figure) image of the umbilical flow.
The Doppler cursor line depicts the ultrasound beam path, which is aligned with the umbil-
ical arterial axis. The sample volume location in a free loop of the umbilical cord is shown.
The lower panel depicts spectral Doppler waveforms from the umbilical artery. The down-
ward vertical arrows point toward the peak systolic and the end-diastolic velocity points
in the wave. The Doppler values are shown on the right.
70 Maulik et al

Fig. 5. Exponential receiver operating characteristic curves of umbilical arterial Doppler

indices. Exponential (E) and receiver (R) values of indices were as follows: resistance index
(RI): E, 10.35; R, 0.629; systolic/diastolic ratio (S/D): E, 8.621; R, 0.661; diastolic/average ratio
(D/A): E, 7.916; R, 0.555; pulsatility index (PI): E, 4.797; R, 0.554. (From Maulik D, Yarlagadda
P, Youngblood JP, et al. Comparative efficacy of the umbilical arterial Doppler indices for
predicting adverse perinatal outcome. Am J Obstet Gynecol 1991;164:1434–40; with
permission.)

value (S), end-diastolic value (D), and the average value over the cardiac cycle (A).
Of the numerous indices, the pulsatility index (PI),13 the resistance index (RI),14 and
the S/D ratio15 are commonly used in obstetric applications. Maulik and co-
investigators used the receiver operating characteristic (ROC) technique (Fig. 6) to
investigate the comparative efficacy of the umbilical arterial Doppler indices for pre-
dicting adverse perinatal outcome and showed that the RI had the best discriminatory
ability when compared with the S/D ratio (P<.05), the PI (P<.001), and the D/A ratio
(P<.05).16 The S/D ratio, however, remains the most popular index.

CLINICAL INTERPRETATION OF UMBILICAL DOPPLER

A systolic diastolic ratio less than or equal to 3.0 or resistance index less than or equal
to 0.6 is considered normal after 27 completed weeks of pregnancy. The benefits of
this technique before 28 weeks of gestation are uncertain. A gestational age-
specific nomogram may also be used. In general, a Doppler index above the 95th
percentile for the gestational age should be considered nonassuring. An initially high
systolic diastolic ratio may progressively decline with advancing gestation, signifying
an improved prognosis. In contrast, a rising index, even within the normal range (<95th
percentile), may indicate worsening fetal prognosis.
The most important diagnostic feature of umbilical artery Doppler waveform is the
end diastolic flow. Absent or reverse end diastolic flow is an ominous finding. The
reverse end diastolic flow carries the worst prognosis for the perinatal come, and
should be interpreted as a late finding. The clinical implications of absence or reversal
of the end diastolic flow in the umbilical artery is further discussed in the next section.
 Umbilical Artery Doppler 71

Fig. 6. Doppler sonography depicting reverse end-diastolic flow in the umbilical artery
(vertical arrows). The upper panel shows the 2-dimensional image of the umbilical artery
and the directed placement of the Doppler sample volume. Color flow in the cord is shown
in gray scale.

DIAGNOSTIC EFFICACY OF UMBILICAL DOPPLER IN FETAL GROWTH RESTRICTION

Diagnostic efficacy of umbilical Doppler in fetal growth restriction can be considered in

terms of diagnosis of FGR or identification of fetal compromise in FGR.
Diagnosis of Growth Restriction
It has been demonstrated that conventional fetal ultrasound biometry is more sensitive
than umbilical arterial Doppler velocimetry in identifying FGR during the antenatal
period.17 This finding should not be surprising because fetal size is expected to be
better assessed by ultrasound measurement of fetal dimensions than by Doppler
velocimetry, which assesses the hemodynamic state; unless the latter is compro-
mised, the Doppler indices will not change.
Adverse Perinatal Outcome
The ability of the fetal Doppler ultrasound to identify fetal compromise in FGR has been
confirmed by numerous investigations over the years, which has been reviewed in
detail elsewhere.18 Most of these studies were focused on the immediate and interme-
diate perinatal outcomes. A few studies have also addressed the neurodevelopmental
outcomes. Farmakides and others19 investigated the diagnostic efficacy of the NST
and of the umbilical arterial S/D ratio in 140 pregnancies. The measures of outcome
included FGR, fetal distress, cesarean delivery for fetal distress, and admission to
the neonatal intensive care unit. Fetuses with a normal NST but abnormal S/D ratio
had an outcome worse than those with an abnormal NST and a normal S/D ratio;
however, those with both tests abnormal experienced the worst outcome.
Maulik and colleagues20 studied the diagnostic efficacy of the umbilical arterial S/D
ratio for predicting adverse perinatal outcome in 350 high-risk pregnant subjects using
the ROC technique and other traditional parameters of evaluating a diagnostic test.
The latter included sensitivity, specificity, and the predictive values. The kappa index
was used to investigate the degree of agreement between the test and the outcome.
The abnormal outcome parameters included small for gestational age (SGA), defined
as less than the 10th percentile; Apgar score at 5 minutes greater than 7; fetal distress
72 Maulik et al

(late and severe variable decelerations, absent variability, fetal scalp pH <7.20); umbil-
ical cord arterial pH less than 7.20; presence of thick meconium; and admission to
neonatal intensive care unit for more than 48 hours. The study indicated that the ratio
predicted the general adverse perinatal outcomes accurately (Table 1).
Fetal Hypoxia and Acidosis
There is also a significant association between abnormal Doppler of fetal circulation
and fetal hypoxia and acidosis as determined by cordocentesis in pregnancies with
FGR. Nicolaides and coworkers21 determined umbilical venous blood gases were
by cordocentesis in 59 fetuses with the ultrasound evidence of FGR (abdominal
circumferences below the fifth percentile for gestational age) who also had absence
of umbilical arterial end diastolic flow. In 88% of the cases the blood gases were
abnormal: 42% were hypoxic, 37% were asphyxiated, and 9% were acidotic. Further-
more, there was a poor correlation between the degree of fetal smallness and acidosis
or the severity of hypoxia. A recent review showed that the correlation coefficients
from several studies ranged from 0.61 to 0.73 for PO2, 0.58 to 0.98 for pH, and
0.48 to 0.90 for lactate.18 The worse the Doppler results get, the stronger the associ-
ation with fetal asphyxia or hypoxia.
Outcome Related to Absent or Reversed End Diastolic Flow
Absence or reversal of end diastolic flow (ARED) in the umbilical artery is an ominous
sign for the perinatal outcome (Fig. 7). The frequency of absent end diastolic flow is
approximately 2% in well-defined, high-risk pregnancies and may be as low as
0.3% in a general obstetric population. This condition is associated with markedly
adverse perinatal outcome, including a high perinatal mortality rate with a higher prev-
alence of chromosomal abnormalities (especially trisomy 13, 18, and 21) and congen-
ital anomalies. In the European multicenter study conducted by Karsdop and
associates involving 245 cases with ARED, the perinatal mortality was 28% and
96% to 98% of the infants required intensive care.22 The chance of developing
ARED was higher in FGR with an odds ratio (OR) of 3.1, and was even greater with
the combination of FGR and hypertension (OR 7.1). The risk of perinatal mortality
was substantially increased with an OR of 4.0 for absent flow and 10.6 for reversed
flow. The mortality rate, however, was also influenced significantly by the gestational

Table 1
Diagnostic efficacy of systolic/diastolic ratio cutoff point of 3.0 to predict the various
abnormal outcomes

Positive Negative
Category Sensitivity Specificity Predictive Value Predictive Value Kappa Index
General abnormal 0.79 0.93 0.83 0.91 0.73
outcome
SGA only 0.75 0.77 0.32 0.95 0.33
Fetal distress, Apgar, 0.86 0.88 0.68 0.96 0.69
pH, NICU
Fetal distress, Apgar, 0.82 0.92 0.81 0.92 0.74
pH, NICU, and
meconium

Abbreviation: NICU, neonatal intensive care unit admission.

Data from Maulik D, Yarlagadda, AP, Youngblood, JP, et al. The diagnostic efficacy of the umbil-
ical arterial systolic/diastolic ratio as a screening tool: a prospective blinded study. Am J Obstet Gy-
necol 1990;162:1518.
 Umbilical Artery Doppler 73

Fig. 7. Umbilical artery Doppler showing reversed end-diastolic flow.

age. More recently, Hartung and others23 also confirmed the role of prematurity as
a significant determinant of the mortality, especially before 32 weeks.
In a review of 1126 cases with absent or reversed umbilical artery end diastolic flow
reported in the literature, it was observed that 170 per 1000 were stillborn and 280 per
1000 died during the neonatal period.24 Most deaths could be attributed to obstetric
complications, such as perinatal asphyxia, growth restriction, prematurity, fetal anom-
alies, and aneuploidy (Table 2).

Neurodevelopmental Outcome
The impact of abnormal fetal and umbilical artery Doppler on short-term and long-term
neurologic sequelae has been investigated. The findings on the short-term outcome
that included neonatal intraventricular hemorrhage and other signs of neurologic injury

Table 2
Absent and reverse end-diastolic frequency in the umbilical artery and adverse perinatal
outcome

Perinatal Outcome Mean Range

Perinatal mortality 45% 17%–100%
Gestational age 31.6 wks 29.0–33.0 wks
Birth weight 1056 g 910–1481 g
Small for gestational age 68% 53%–100%
Cesarean section for fetal distress 73% 24%–100%
Apgar score at 5 min <7 26% 7%–69%
Admission to neonatal intensive care unit 84% 77%–97%
Congenital anomalies 10% 0%–24%
Aneuploidy 6.4% 0.0%–18.0%

Data from Maulik D. Doppler ultrasound in obstetrics. In: Cunningham FG, et al, editors. Williams
Obstetrics. 19th edition. Stamford CT: Appleton & Lange, Suppl 16.
74 Maulik et al

have been contradictory. In this interpretation, the confounding influence of prematu-

rity on the neurologic outcome must be considered.25 The long-term outcome
included various measures of neurodevelopmental status. Ley and Marsal26 recently
reviewed the effects of abnormal fetal or umbilical Doppler on neurologic outcome.
It is apparent that abnormal umbilical artery and fetal aortic Doppler results are asso-
ciated with long-term neurodevelopmental compromise. In a recent prospective
observational study in pregnancies with FGR, Baschat and colleagues27 investigated
the relationship between fetal Doppler (umbilical artery, middle cerebral artery, and
ductus venosus), BPP, and neurodevelopmental outcome at 2 years of age. Of the
various fetal tests, only the UA reverse end diastolic flow independently predicted
poor neurodevelopment in FGR. Not surprisingly, extreme prematurity and birth
weight were the major predictors of poor neurodevelopmental outcomes.

UMBILICAL DOPPLER IN MULTIPLE GESTATIONS WITH GROWTH RESTRICTION

Fetal Doppler may be beneficial in managing multi-fetal gestations complicated with

twin growth discordancy and those with twin transfusion syndrome. A comprehensive
and current review of the Doppler in multiple gestations is available elsewhere.28
Gaziano and associates29 observed that in 94 twin pairs and 7 sets of triplets, an
abnormal pulsed Doppler velocimetry showed high correlation with adverse preg-
nancy events and that those with abnormal Doppler findings tended to be born 3 to
4 weeks earlier and exhibit a greater number of stillbirths, malformations, and greater
morbidity. Giles and colleagues30 noted a fall in the corrected perinatal mortality from
42.1in 1000 to 8.9 in 1000 in an observational study. However, they also reported
a multicenter randomized controlled trial (RCT) of umbilical artery Doppler in 526
women with twins that did not show any improvement in the perinatal mortality, but
did show that close monitoring in twin gestation is associated with a lower-than-
expected fetal mortality in both the control and the Doppler groups.31
Quintero and coworkers32 demonstrated the prognostic value of a staging system
for twin transfusion syndrome that includes Doppler ultrasound of the umbilical artery,
umbilical vein, and ductus venosus, along with other ultrasound findings. The staging
was proposed for individualizing the treatment options, especially the laser ablation
procedure, and has become widely accepted in managing this complication.

CLINICAL EFFECTIVENESS OF UMBILICAL DOPPLER IN FETAL GROWTH RESTRICTION

A diagnostic test is clinically effective if its use in the indicated clinical situation
improves the outcome. This inference requires an unbiased demonstration that its
use for any intervention actually works. Such a demonstration is accomplished by
appropriately conducted randomized clinical trials and constitutes the level I evidence
of effective care.
Regrettably, clinical effectiveness of most fetal monitoring tests has not been suffi-
ciently investigated by clinical trials before their introduction into clinical use. However,
umbilical Doppler has been subjected to extensive verifications of its clinical effective-
ness by RCTs and their systemic review by meta-analysis.
Randomized Clinical Trials
By the time of this publication, there have been 21 published trials on umbilical and
fetal Doppler sonography.31,33–52 One of the studies is no longer included in any
considerations because of the concerns related to scientific integrity. The remaining
20 studies involving a total population of approximately 25,000 women have been
reviewed in detail elsewhere53 and summarized in Table 3. Additional studies have
 Umbilical Artery Doppler 75

Table 3
Published randomized trials of umbilical artery Doppler ultrasound in high-risk, low-risk, and
unselected populations

Author, Year Population Better

(References) (Risk Category) Doppler Index Doppler in Controls Outcome
Trudinger et al, 198733 300 (high risk) UA S/D Concealed Yes
Tyrrell et al, 199035 500 (high risk) UA S/D Selective Yes
Ut S/D
Hofmeyr et al, 199136 897 (high risk) UA S/D Selective No
Newnham et al, 199137 505 (high risk) UA S/D Concealed No
Ut S/D
Alstrom et al, 199238 426 (high risk) UA BFC No Doppler Yes
Davies et al, 199239 2475 (unselected) UA S/D No Doppler No
Ut S/D
Mason et al, 199340 2025 (unselected) UA S/D No Doppler No
Johnstone et al, 199341 2289 (high risk) UA RI No Doppler No
Newnham et al, 199342 2834 (unselected) UA S/D Selective No
Ut S/D
Whittle et al, 199443 2986 (unselected) UA S/D Concealed Yes
Pattinson et al, 199444 212 (high risk) UA S/D Concealed Yes
Omtzigt et al, 199445 1598 (unselected) UA S/D No Doppler Yes
Nienhuis et al, 199746 150 (high risk) UA PI Concealed No
Doppler French Study 4187 (low risk) UA RI No Doppler No
Group, 199747
Haley et al, 199748 150 (high risk) UA S/D No Doppler No
Ott et al, 199849 665 (high risk) UA S/D / 11% UA S/D Yes
MCA S/D
McCowan et al, 200050 167 (high risk) UA RI MCA RI No
UTA RI
Williams et al, 200351 1340 (high risk) UA S/D No Yes
The GRIT Study Group, 547 (high risk) UA EDV Post-test No
200352 randomization
Giles et al, 200331 526 (twins) UA S/D No Doppler No

Abbreviations: BFC, blood flow classes; EDV, end-diastolic flow velocity; MCA, middle cerebral
artery; Uta, uterine artery.
Data from Maulik D, Figueroa R. Doppler velocimetry for fetal surveillance: randomized clinical
trials and implications for practice. In: Maulik D, editor. Doppler Ultrasound in Obstetrics and Gyne-
cology. Springer: Germany; 2005. p. 387–402.

been reported only in the abstract form or conference presentations. Finally, one
multicenter randomized trial known as the Trial of Umbilical and Fetal Flow in Europe
(TRUFFLE) is nearing completion and the results were not available by the time of
writing this article.
These trials have many limitations, including inadequate sample size, heteroge-
neous selection criteria, study objectives, randomization process, Doppler method,
and frequent absence of any explicit management policy. Obviously, it would have
been preferable to have one or a few randomized trials that are well powered, well
designed, and well conducted consistent with rigorous guidelines for such studies.
Despite these concerns, it is noteworthy that most trials conducted in high-risk pop-
ulations showed improved outcome.
76 Maulik et al

Meta-analysis of Doppler Trials

To mitigate against the previously mentioned limitations, meta-analyses or systemic
reviews of the fetal and umbilical Doppler RCTs have been conducted. The purpose
of meta-analysis is to aggregate and statistically analyze data from multiple selected
clinical trials to derive valid quantitative conclusions. Several such meta-analyses
have been reported since the early 1990s with newer analyses incorporating more
recent RCTs.
Alfirevic and Neilson54 published the first meta-analysis that included 12 RCTs con-
ducted in high-risk pregnancies. For perinatal mortality, they observed an OR of 0.62
with 95% confidence interval (CI), 15% to 55% indicating a 38% decline in the risk.
The reductions were noted in both fetal deaths and neonatal deaths. Post hoc anal-
yses revealed significant decreases in elective delivery, intrapartum fetal distress,
and hypoxic encephalopathy in the Doppler group. The investigators concluded that
there was “compelling evidence that women with high-risk pregnancies, including
preeclampsia and suspected intrauterine growth retardation, should have access to
Doppler ultrasonographic study of umbilical artery waveforms.”54
Another meta-analysis looked at only trials involving high-risk pregnancies where
there were guidelines for the use of Doppler data in the clinical management.55 Only
3 studies were identified with a total of 1575 subjects at the time. An average of
80% reduction in fetal deaths without malformations was noted (OR, 0.19; 95%
CI 0.06–0.63).
Westergaard and colleagues56 included only well-defined, high-risk pregnancies.
Out of a total of 13 trials of Doppler in high-risk pregnancies, only 6 had defined
FGR and pregnancy hypertension as indications for surveillance. In the well-defined
trials, there were significantly higher preventable perinatal deaths in the Doppler
than in the control group (50% and 20%, respectively).
The most recent Cochrane review57 included 18 completed trials encompassing
more than 10,000 subjects. The review demonstrated a 29% decrease in perinatal
mortality, which was significant with a risk ratio (RR) of 0.71 and a 95% CI of 0.53
to 0.98. This finding meant that 203 women needed to be treated for preventing 1 peri-
natal death. There were also less impressive but significant decreases in inductions of
labor (RR 0.89, 95% CI 0.80–0.99), and cesarean deliveries (RR 0.90, 95% CI 0.84–
0.97). No significant effects were noted in operative vaginal deliveries or Apgar scores
less than 7 at 5 minutes.
In summary, most randomized trials of umbilical artery Doppler in high-risk pregnan-
cies demonstrated a clinically and statistically significant improvement in the perinatal
mortality (level I evidence), which makes it unique among the other fetal monitoring
modalities.

OTHER TESTS OF FETAL SURVEILLANCE IN FETAL GROWTH RESTRICTION

Although Doppler sonography of ductus venosus, middle cerebral artery, and uterine
artery has shown significant diagnostic efficacy, its clinical effectiveness has not been
adequately investigated. Ductus venosus Doppler does provide an additional tool for
assessing serious fetal compromise and has been used by many in clinical practice
(level II, III). The effectiveness of ductus venosus Doppler in improving the outcome
is under investigation at present in the TRUFFLE study (see previous discussion).
These additional Doppler methods are beyond the scope of this article. Antepartum
fetal heart rate monitoring and BPP, or its modifications, still remain the main stay
of fetal surveillance. Although the diagnostic efficacy of these tests has been demon-
strated over the decades, there is insufficient evidence for their effectiveness in
 Umbilical Artery Doppler 77

improving the outcome. However, their usefulness has been shown in clinical experi-
ence and they remain an essential part of the standard of practice in fetal surveillance
(level II, III).
There is a compelling reason to use multiple tests of fetal well-being in high-risk
pregnancies as fetal decompensation involves multiple systems. As discussed earlier,
this is reflected in the hierarchical sequence of fetal deterioration in placental insuffi-
ciency. The previous observations may provide the basis for determining the optimal
choice, combination, or sequence of fetal testing in managing FGR.

UMBILICAL ARTERY DOPPLER IN MANAGING FETAL GROWTH RESTRICTION

Umbilical artery Doppler has been shown to be beneficial in clinical conditions char-
acterized by placental insufficiency and consequent chronic nutritive and hypoxic
stress of the fetus. Specifically, the technique is effective in reducing perinatal deaths
and unnecessary obstetric interventions in pregnancies complicated by fetal growth
restriction or preeclampsia (level of evidence I). It may also be effective in monitoring
multiple pregnancies, especially those suffering from discordancy, growth restriction,
and twin transfusion syndrome.
There is uncertainty regarding its effectiveness in managing other high-risk preg-
nancies, although several randomized trials performed included women with mixed
high-risk pregnancy conditions.

Initial Management
Once the diagnosis of FGR has been confirmed by fetal biometry, the clinical manage-
ment path consists of several steps as subsequently outlined. This discussion is
focused on the fetal surveillance aspect of the management.
Initially, care should be taken to rule out fetal malformations and aneuploidy, which
requires individualized management, including the determination of fetal karyotype. If
lethal malformations and aneuploidy are identified, fetal surveillance and unnecessary
interventions should be avoided as they may expose the mother to unjustifiable risks.
Fetal growth should be followed serially as discussed previously in this issue. Fetal
ultrasound growth profile may also be used as an indicator of fetal well-being as
complete cessation of growth in consecutive biometry over 2 to 4 weeks is considered
ominous.
In pregnancies complicated with FGR, fetal surveillance should consist of weekly
umbilical Doppler (level A recommendation). Some form of BPP or NST should be
used either as a backup test or simultaneously with the umbilical artery Doppler (level
B recommendation). There is significant rationale, however, to follow the latter course
of simultaneous testing because of the multisystem nature of the fetal compromise
(see previous discussion).
Fetal monitoring should be intensified if there is a worsening of the clinical status,
(eg, a progressive decline in the fetal growth rate by biometry, oligohydramnios, or
preeclampsia) and appropriate obstetric intervention according to the existing stan-
dards of practice should be implemented. This subject is further discussed later. If
the fetal and the maternal evaluations remain reassuring, the pregnancy can continue
to fetal maturity at which point delivery should be accomplished (level A and B
recommendation).

Management with Elevated Umbilical Artery Doppler Indices

If the umbilical Doppler index is high or increasing, more intensive fetal surveillance is
warranted with weekly umbilical Doppler ultrasound and twice per week NST, BPP, or
78 Maulik et al

modified BPP. The end diastolic flow may transiently improve, and days to weeks may
elapse before the fetus shows additional evidence of compromise, especially in
preterm gestation. However, fetal risk of an adverse outcome still remains elevated.
Intense monitoring of fetus as previously outlined should be instituted (level A and B
recommendation).
If fetal surveillance tests indicate fetal compromise (eg, nonreactive NST, poor fetal
heart rate baseline variability, persistent late decelerations, oligohydramnios, or BPP
score <4), delivery should be strongly considered, with the mode of delivery deter-
mined by the overall clinical considerations. Again, in most instances, cesarean
delivery should be preferred (level A and B recommendation).

Management with Absent End Diastolic Flow

As absent or reverse end diastolic flow in the umbilical artery is associated with poor
perinatal outcome, an urgent clinical response is indicated. The specific management
of severe Doppler abnormalities will be guided by the gestational age.
If the gestational age is greater than 34 completed weeks, when the risk of fetal lung
immaturity is less than that of intrauterine asphyxia to the fetus, development of
absent end diastolic flow should prompt immediate consideration for delivery (level
A recommendation).
In preterm pregnancies, with the gestational ages between 28 to 34 completed
weeks, the management is more conservative because prematurity is a significant
concern. The fetus should be monitored daily with umbilical artery Doppler, NST,
and BPP (or modified BPP). In addition, ductus venosus Doppler may also be used
as an additional backup test with the absence or reversal of the a wave indicating
serious fetal compromise. However, its effectiveness in improving the outcome has
not yet been demonstrated (see TRUFFLE study previously discussed). Betametha-
sone should be given to promote fetal pulmonary maturity. Delivery is indicated
when one or more of these tests indicate imminent fetal danger, regardless of maturity.
The presence of reverse flow at any gestational age beyond 28 weeks should prompt
immediate delivery (level A and B recommendation).
In extreme prematurity, with gestational ages less than 28 completed weeks, the
optimal timing for delivery remains uncertain. The multicenter Growth Restriction Inter-
vention Trial (GRIT) involving high-risk preterm pregnancies failed to resolve this issue.
In this study, no significant differences were noted in the deaths before discharge from
the hospital between the early and the delayed delivery groups. In a follow-up study,
no important differences in mortality or in the developmental assessment were seen at
or beyond 2 years of age.58 As a higher rate of disability was observed in early preterm
births, the investigators cautioned against early delivery in this group. Until new
evidence emerges, a pragmatic approach is advised in this group with individualized
plan of care that would consider the relevant clinical factors along with appropriate
counseling of the mother and the family (level B recommendation).

INTRAPARTUM MANAGEMENT

During labor, continuous fetal monitoring consistent with the current standard of prac-
tice should be followed. Any management decision will depend on a comprehensive
assessment of the clinical situation, including fetal status, gestational age, obstetric
factors, and associated pregnancy complications. In general, when the intervention
is dictated by deteriorating fetal status, especially in the presence of absent or reverse
end diastolic flow in the umbilical artery Doppler, cesarean delivery may be the
 Umbilical Artery Doppler 79

prudent choice because fetal tolerance to labor is expected to be poor (level A and B
recommendation).

SUMMARY

In conclusion, Doppler velocimetry of the umbilical artery provides an effective, nonin-

vasive fetal monitoring tool that allows assessment of fetoplacental hemodynamic
state and fetal prognostication in growth restricted pregnancies. Umbilical artery
Doppler indices indirectly reflect impedance of downstream circulation and have
been correlated with deficient development of fetoplacental vascular system in FGR
pregnancies. Many investigators have shown the efficacy of abnormal Doppler indices
in predicting fetal hypoxia, fetal acidosis, and adverse perinatal outcomes (level of
evidence II). Most randomized trials and systemic reviews of umbilical artery Doppler
ultrasound show improved outcome in pregnancies complicated by FGR (level
of evidence I). Clinical management of FGR should integrate the Doppler
approach with existing modalities of antepartum fetal monitoring (level A and B
recommendation).

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