Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5796_Библиотеки_им_академика_М_И_Перельмана.pdf
430
Chapter 15 Fetal Cerebral Circulation
MCA branches
MCA
A
Figure 15–4. Conventional 3D power Doppler image of fetal brain
circulation. (A) Cranial view. The bilateral internal carotid arteries (ICA)
and middle cerebral arteries (MCA), as well as the branches of MCA, are
demonstrated. (B) Anterior oblique view. The anterior cerebral artery
(ACA) and the pericallosal artery (PcA) are demonstrated.
ICA
B
PcA
ACA
will provide those images. These are excellent teaching
materials. Figure 15–7 shows such reconstructed 3D
angiography of normal cerebral circulation at 31 postmenstrual weeks.
Tomographic US imaging is useful for obtaining
orientation of cerebral vessels. High-frequency TVS
employing a 6 to 12 MHz transducer (Voluson E8,
GE Healthcare, Waukesha, Wisconsin) has enabled the
demonstration of vessels on the cerebral pial surface,
as shown in Figures 15–8 and 15–9 . Furthermore, the
author (RKP) succeeded in demonstrating the fine med-
Middle
cerebral
Circle of
Willis
Figure 15–5. Fetal brain vascularity at 20 postmenstrual weeks.
(A) Coronal lane. (B) Median plane. (C) Axial/horizontal plane. (D) 3 D
angiographic rendering. ACA, anterior cerebral artery; PCA, pericallosal
artery. (Courtesy of Timor-Tritsch et al.)
Pericallosal
artery
ullary vessels running from the pial surface toward the
subependymal area by bidirectional power Doppler with
3D angiostructural imaging,
7 , 13
as shown in Figure 15–10 .
As seen on these images, 3D imaging technology with
high-frequency TVS and 3D power Doppler allows the
images to be assessed on the orthogonal display as well as
on the rendered planes. Conventional 3D power Doppler
technology could not depict small-caliber blood vessels;
however, recent advances in 3D technology using bidirectional power Doppler allows tiny blood vessels to be
depicted.
Corpus callosum
A
Figure 15–6. Anterior cerebral artery and its branches in a 24 postmenstrual weeks’ normal brain (median view). (A) Two-dimensional (2D) power
Doppler image by B-mode demonstrates the corpus callosum (CC). (B) 3D reconstructed angiographic image. ACA, anterior cerebral artery; CMA, callosomarginal artery; SSS, superior sagittal sinus. The cingular branch of the CMA runs along the cingulate gyrus.
Cingular branch of CMA
SSS
B
ACA branches
CMA
ACA
Chapter 15 Fetal Cerebral Circulation
AB
Figure 15–7. 3D tomographic ultrasound (US) image of brain circulation at 31 postmenstrual weeks. (A) Tomographic power Doppler imaging of
serial sagittal sections on which the anterior cerebral arteries and their branches are seen. The image at the center represents the perfect median section.
(B) Successive and serial coronal sections. The middle cerebral arteries and their branches are seen on these sections.
431
Using this technique, medullary vessels are detectable
from the early second trimester developing into numerous “showerlike” vessels. Before 20 weeks, as seen in
Figure 15–9 , the medullary veins are demonstrated as red
color or red/blue colors by bidirectional power Doppler,
and thereafter remarkably rapid development is seen in the
previously mentioned showerlike vessels ( Figure 15–11 ).
In the fetal brain, the medullary vessels within the deeper
cerebral white matter are more developed than the
subcortical veins located within the subcortical white
14
matter.
The maldevelopment of medullary vessels may
indicate developmental abnormalities and may predict
subsequent hydrocephaly and postnatal neurologic deficit. At this time we have no scientific proof of the clinical
importance of this fascinating display of the fine details of
A
B
C
fetal brain circulation. The author (RKP) has been investigating the assessment of medullary veins in normal and
abnormal brain structure. It is expected that the investigation will be one of the clues in evaluation of the relations
between the fetal brain development and postnatal neurologic findings.
A
Gyri
Sulcus
B
Figure 15–8. Reconstructed 3D angiography of normal cerebral circu-
lation at 31 postmenstrual weeks. 3D bidirectional power Doppler angiograms of sagittal ( A ), coronal ( B ), and axial ( C ) sections.
Figure 15–9. Coronal view of pial vascularity along the cerebral sulci
and gyri by 3D bidirectional power Doppler angiography at 33 postmenstrual weeks of gestation. (A) 3D bidirectional power Doppler angiogram
of pial vessels along the gyri and sulci. (B) 3D reconstructed image of the
cerebral by surface y gray scale. Protrusion of the brain surface due to
gyral formation is demonstrated.
432
Sulcus
AB
Figure 15–10. Parietal/tangential view of pial vascularity along cerebral
sulci and gyri by 3D bidirectional power Doppler at 30 weeks of gestation.
(A) 3D reconstructed gray scale image of the cerebral surface. Falx cerebri
and gyral formation are well demonstrated. (B) 3D bidirectional power
Doppler sonoangiogram of superficial vascularity and pial vessels along
the gyri and sulci. SSS, superior sagittal sinus.
Chapter 15 Fetal Cerebral Circulation
SSS
Gyrus
Falx
cerebri
TECHNICAL CONSIDERATIONS
AND DOPPLER CRITERIA
For studying the MCA according to anatomical data, Mari
and collaborators
cerebral peduncles in the section containing the pons and
the medulla oblongata and greater paired wings of the
sphenoid. It can also be visualized at the level of the cerebral peduncles at its anterolateral border, running anterolaterally toward the lateral edge of the orbit.
The base of the skull at the level of the temporal and
sphenoidal bones is the preferred plane for recording
Doppler signals from the ACA and PCA. The ACA flowvelocity waveforms can be obtained close to the midline,
anterior to the pulsating ICA, and half the distance from
the midbrain to the frontal bone. The PCA recordings are
done at the level of the transverse cerebral fissure on the
side of the midbrain.
Using the transabdominal route, a prerequisite for
recording cerebral Doppler signals is that the head is not
too deeply engaged in the maternal pelvis.
scanning of cerebral vessels was recommended by
Lewinsky et al.
approach showed separate and easily distinguishable
images of these arteries, because the ICAs are located
medially and inferiorly to the corresponding MCAs. With
the use of a transfontanelle approach in the newborn,
detection of flow is easily obtained from the ACA, where
it curves around the corpus callosum.
of the fetal cerebral circulation, Doppler-derived data
15
suggested a plane more caudal to the
16
Transvaginal
17
The coronal section obtained by this
18
In most studies
19w 24w
M
Figure 15–11. Development of medullary vessels with advanced gestational age. 3D reconstructed coronal power Doppler images from the same fetus
at 19 postmenstrual weeks of gestation ( A ) and 24 postmenstrual weeks ( B ). At 19 postmenstrual weeks, medullary vessels (M) are immature, and most
of the veins run toward the pia mater. With advancing gestational weeks, medullary vessels (M) mature and increase in numbers. The vessels run in the
central direction from the cerebral cortex toward the longitudinal caudate vein of Schlesinger (S).
M
M
S
M
S
Chapter 15 Fetal Cerebral Circulation
433
are gained from the MCA and ICA due to the ease of
obtaining recordings. Few studies have reported on data
collected from other cerebral vessels (ie, the ACA and
19 – 21
PCA).
data, the same vessels should be studied.
To correlate fetal with neonatal cerebral flow
22 , 23
Detection of vessels is based on visualization of pulsatile
flow-velocity waveforms with duplex systems or by using
color flow imaging.
24
Transducers with carrier frequencies
of 2.5, 3.5, and 5 MHz are usually used, the sample gate
not exceeding 3 to 4 mm. This allows clear flow-velocity
signals without interference from other nearby vessels. A
high-pass filter of 50 to 150 Hz is applied to remove signals
originating from slow-moving tissues in the path of the
Doppler beam. The angle of insonation is kept as small as
possible, and the low-power output mode should be used
throughout the study. For standard conditions, all samples
are taken with subjects in the semi-recumbent position
and during fetal apnea, as high-amplitude fetal breathing
modulates the blood flow.
25
For calculation of qualitative Doppler indices, velocity
waveforms are recorded, and peak velocity, end-diastolic
velocity, and mean maximum velocity are measured. Three
to five consecutive waveforms are analysed, and the results
are averaged. Using these Doppler variables, the pulsatility
index (PI), defined as the difference between the PSV and
end-diastolic value divided by the mean maximum flow
velocity,
agreement and intraobserver repeatability were found for
cerebral vessels studied.
26
may be calculated. Substantial interobserver
27 , 28
Other qualitative parameters may be determined
but are less frequently used: the ratio of peak systolic to
maximum end-diastolic velocity (S/D ratio), the resistance index (RI) (the difference between peak systolic and
end-diastolic velocities divided by the PSV), and the cerebral index (PSV minus S/D ratio).
29
Ratios of qualitative
parameters in other fetal vessels are also in use: the ratio
of RI in the fetal common carotid artery to the RI in the
umbilical artery, as described by Arabin et al,
between the cerebral RI and the placental RI, as described
by Arbeille and colleagues.
21
The use of color flow imag-
30
or the ratio
ing enables accurate measurement of the angle of vessel
insonation to determine absolute mean blood flow velocity
values in intracranial vessels.
31
The venous circulation of the fetal brain can be identified by color Doppler. Recently, the US-anatomical correlates were established for the venous blood flow in the fetal
brain, and the reference values for flow-velocity waveforms
in the transverse sinus were documented.
32
Power Doppler improves the sensitivity of detection
of the presence of flow, when compared with conventional color Doppler velocity imaging. Fetal intracerebral
arteries and veins that could not have been imaged
by the transabdominal approach were demonstrated
using a combination of TVS and power Doppler flow
mapping.
4
Normal Fetuses
The intracranial circulation becomes visible as early as
the 8th week of pregnancy, when arterial pulsation can
be detected on an axial view of the embryonic skull. In
a study by Kurjak and coworkers
33
using transvaginal
US, the visualization rate of pulsation on the base of the
skull increased from 50% at the 8th gestational week to
83% at the 10th week. From the 11th week onward, it
became a constant finding. It is very difficult to distinguish blood flow between the various cerebral arteries
because the distances are in a range of a few millimeters
or even less. The waveform signal profile at this gestational age is characterized by the absence of an enddiastolic component.
During the third trimester, continuous flow is present
throughout the cardiac cycle in the ICA, confirming the
existence of low peripheral vascular resistance in the fetal
34
Flow-velocity waveforms from the fetal MCA are
brain.
highly pulsatile, and the presence of end-diastolic frequencies becomes more common with advancing gestation.
31
Thus, end-diastolic frequencies were present in 75% of
fetuses at 18 to 25 weeks and in all fetuses examined after
34 weeks’ gestation.
The PI of the MCA was found to be higher than that
for either the ICA or the proximal ACA.
31
15
Hata et al
35
found the RI of the PCA to be lower than that of the MCA
and ACA.
These differences emphasize the need for an exact
definition of the vessel that is being insonated and could be
caused by different resistances in various portions of the
cerebral circulation. In vitro examination of the contractile properties of the common carotid artery in the fetal
lamb has shown that this vessel has less dilating capacity
in response to hypoxia than do the intracranial arteries.
36
However, in cross-sectional studies, mean blood flow
velocities in the common carotid artery increased throughout pregnancy in contrast to aortic velocities, which tend
to decrease toward the end of pregnancy. The PI in the
aorta remains constant, whereas in the common carotid
artery, it falls steeply after 32 postmenstrual weeks.
nificant decrease in the PI was also observed in the MCA,
especially after 36 weeks ( Table 15–1 )
38 – 40
37
A sig-
. These results
suggest that with advancing gestation there is redistribution of the fetal circulation, with decreased impedance
to flow to the fetal brain, presumably to compensate
for the progressive decrease in fetal blood PO 2 . In studies
of the MCA in the second trimester,
was found until the late second trimester, followed by a
decline in the third trimester. Mari and Deter
41 – 43
an increasing PI
43
attributed
the low PI values at the beginning and end of pregnancy
to increased metabolic requirements and therefore lower
cerebral vascular impedance to blood flow.
Studies of waveforms recorded from the fetal ICA
demonstrated that the PI remains fairly constant during the last trimester of pregnancy, and only during the
last 4 weeks does there seem to be a slight decrease.
31
Reference RIs of the fetal MCA were established in a large
and minimally selected population attending a single clin-
44
ic.
Cerebral vascular resistance decreases constantly up to
gestational week 42.
In a longitudinal study,
44
22
fetal and neonatal cerebral blood flow velocities were assessed in the MCA
in 40 uncomplicated pregnancies during the third
434
Chapter 15 Fetal Cerebral Circulation
Table 15–1. PULSATILITY INDEX OF THE MIDDLE CEREBRAL ARTERY IN NORMAL FETUSES
AS A FUNCTION OF GESTATIONAL AGE: REGRESSION EQUATIONS
Authors Regression Equation r
Van den Wijngaard and colleagues
Arstrom and colleagues
Arduini and Rizzo
Mari and Deter
PI, pulsatility index; GA, gestational age; r2, coefficient of determination.
Reproduced from Marsal and colleagues, 1994,71 with permission.
PI = −3.44 + 0.36 × GA − 0.006 × GA
PI = 5.13 − 0.09 × GA
PI = 0.006 + 0.144 × GA − 0.003 × GA
PI = 1.97 + 0.327 × GA − 0.006 × GA
trimester and in 22 neonates born from these pregnancies ( Table 15–2 ). PSV, temporal mean, and end-diastolic
flow velocities increased during the third trimester and
were significantly higher from 36 weeks’ gestation on,
as compared with values obtained at 28 postmenstrual
weeks, suggesting an increase in actual blood flow. The PI
PHYSIOLOGIC VARIABLES
AFFECTING CEREBRAL BLOOD
FLOW IN NORMAL PREGNANCY
The physiologic changes to cerebral blood flow in normal
pregnancy are summarized in Table 15–3 .
2
2
2
and RI of the MCA did not differ significantly during this
period. Immediately after birth, flow velocities decreased
significantly and remained lower during the first 5 postnatal days compared with fetal values. The PI and RI of
the MCA tended to decrease during the first postnatal
day but stabilized afterward. These alterations in cerebral
blood flow in the transition from the fetal to the neonatal
state are explained by local rather than central cardiovascular changes, mainly the local effect of oxygen on
peripheral vessels.
45
Doppler flow studies in twins without growth retardation or discordance demonstrated changes throughout
pregnancy similar to those in singletons.
46 , 47
Fetal Heart Rate
An inverse correlation was found between fetal heart rate
and PI in the MCA of fetuses with heart rate decelera-
48
and with tachycardia secondary to ritodrine infu-
tions
49
sion.
Within the normal range of fetal heart rate, Doppler
indices did not alter significantly.
Fetal Breathing Movements
High-amplitude fetal breathing movements modulate flowvelocity waveforms in the fetal ICA.
2
— 51
0.52 173
0.52 41
0.45 43
References
50
This is similar to
Table 15–2. REFERENCE VALUES FOR DOPPLER INDICES OF CEREBRAL VESSELS
IN THE THIRD TRIMESTER OF PREGNANCY
Vascular Index 26 to 27 Weeks* 40 Weeks* References
Common carotid artery pulsatility index
Internal carotid artery pulsatility index
Middle cerebral artery
Pulsatility index
Systolic/diastolic ratio
Resistance index
Mean velocity (cm/sec)
Anterior cerebral artery resistance index
Posterior cerebral artery resistance index
*Postmenstrual weeks.
Reproduced from Degani and colleagues, 1988,
118
with permission.
2.13 ± 0.11 1.89 ± 0.07
1.63 ± 0.35 1.31 ± 0.41
2.30 ± 0.48 1.82 ± 0.38
6.89 ± 1.48 4.23 ± 0.67
0.93 ± 0.049 0.68 ± 0.087
5.3 ± 2.3 11.3 ± 3.1
0.83 ± 0.05 0.79 ± 0.04
0.73 ± 0.05 0.70 ± 0.06
37
33
31
68
35
31
172
118
Chapter 15 Fetal Cerebral Circulation
Table 15–3. CHANGES IN IMPEDANCE CRITERIA (PULSATILITY AND RESISTANCE INDICES) IN FETAL CEREBRAL
ARTERIAL VASCULATURE SECONDARY TO VARIOUS PHYSIOLOGICAL AND NONPHYSIOLOGICAL
STATES IN PREGNANCY
Impedance
435
Internal
Carotid
State
Artery
Gestational age
↑ Fetal heart rate ↓
↓ Fetal heart rate ↑
Fetal breathing movement
↑/↓
Fetal behavior stage 2F
Plasma glucose concentration
Fetal head compression
Uterine contractions
Fetal anemia
↑/N ↑/↓
↑/N ↑/N
Oilgohydramnios
Growth retardation
↓↓ ↓↓/↓↓ ↓ ↑
Fetal hydrocephaly
Arteriovenous malformation —
↑ Pco
2
↓ Pco
2
↑, Increased; ↓, decreased; N, normal.
a
Depending on fetal behavior stage.
Reproduced from Degani, and colleagues, 1988,
Middle
Cerebral
Artery
Anterior
Cerebral
Artery
Posterior
Cerebral
Artery
Mean Blood
Velocity References
↓ N/↓ ↓ ↓↓ ↑
——— —49
— — — — 48, 49
——— —50
↓
↑↓/↑
↑↑
——— —52
a
— — — 53, 54, 56
—— —57
— — — 60–62
——
↑↑
↑↑/N/↓
↓
↓↓
↓↓
118
with permission.
— — — 58, 90–94
— — — 118–120
— — — 156–157
— — — 133, 134
——
31, 33, 37, 39, 46, 47
↑
64, 65
15, 17, 21, 29, 31, 43, 68, 69
↑
31, 69
findings in the umbilical artery and vein and fetal descending aorta, where changes in PI ranging from –25% to +30%
have been observed.
25
It is recommended, therefore, that
cerebral flow-velocity waveforms be recorded under a
standardized condition (eg, a period of fetal apnea).
Fetal Behavioral States
Nijhuis et al
fetus from 36 weeks on. Based on changes in fetal heart
rate patterns, body movements, and eye movements,
four states were defined. Doppler flow-velocity waveforms recorded from the fetal ICA in normal pregnancies at 37 to 38 weeks’ gestation during fetal behavioral
states 1F (quiet sleep) and 2F (active sleep) demonstrated
a significant reduction of the PI in state 2F compared
with that in state 1F.
related to heart rate only and could be demonstrated at
50
described behavioral states in the human
52
This reduction of PI was not
standardized heart rate. Increased oxygen demand during fetal activity is followed by increased cerebral blood
flow, reflecting autoregulation. It is suggested that fetal
neurologic development expressed by the emergence of
fetal behavior is associated with specific hemodynamic
adaptation.
Plasma Glucose Concentration
We found a significant positive correlation between maternal plasma glucose concentration and the PI of the ICA.
Similar changes were demonstrated in the fetal MCA after
a glucose challenge test.
mia was found to be associated with an increase in cerebral
blood flow.
55
This may be a compensatory mechanism to
54
In preterm infants, hypoglyce-
maintain glucose supply to the brain.
An indirect effect, mediated through induced changes
in behavioral state, was suggested by others.
56
53
436
Chapter 15 Fetal Cerebral Circulation
Fetal Head Compression
The increase in the PI of flow-velocity waveforms from the
MCA was found to be associated with maternal abdominal
pressure, even from the US transducer,
polyhydramnios,
59
or uterine contractions during labor.
57
olighydramnios,
58
60
Fetal head compression was suggested as the underlying
mechanism of these changes. End-diastolic flow velocities
are reduced, and in some cases reverse diastolic flow is
seen.
Transvaginal Doppler assessment of the fetal MCA
could not confirm a change in peripheral resistance in the
fetal cerebral vascular bed during the first stage of normal
61 , 62
labor.
The growing list of internal and external variables affecting cerebral circulation emphasizes the need for
strict standards in study design.
Labor and Delivery
Fetal aortic blood flow was demonstrated to be increased
with the progress of labor.
seems to remain unaffected by uterine contractions.
However, conflicting results are reported on changes in
fetal cerebral vascular resistance during and between contractions. Yagel and collaborators
40% in vascular resistance in the fetal MCA during labor.
Their hypothesis suggests a protective mechanism to prevent fetal cerebral hypoxia.
During contractions, increased PI values were found
in the fetal ICA,
66
ACA
and MCA.
60
but no difference was found in the
61
The varying results may be related to
other variables (eg, the intensity of the contractions, the
fetal head position and station, or the degree of molding
of the skull).
In pregnancies complicated by preterm labor with
intact membranes, significantly reduced PI values
from the MCA were recorded when compared with
fetuses delivered later or normal reference limits for
gestation.
67
The mode of delivery does not seem to influence
cerebral blood flow velocities in healthy term newborns.
Decompression of the fetal head during vaginal delivery
may influence cerebral blood flow. Marsal et al
Maesel et al
and low resistance values at the moment of birth. Ipsiroglu
and associates,
72
found a very high cerebral blood flow velocity
73
in a study of infants delivered by cesarean section, reported the highest blood velocities among
infants after prolonged and difficult delivery of the head.
56
The umbilical circulation
60
found a reduction of
71
and
64 , 65
70
increased velocity to anemia was not affected by the PI;
therefore, these authors suggest that the hyperdynamic
circulation is a consequence of decreased blood viscosi-
75
ty.
Increased PSV in the MCA was found to be reliable in
detecting anemia in pregnancies complicated by maternal
blood group immunization.
76
Intravascular transfusion to
correct anemia was not associated with a significant difference in the PI values of cerebral vessels when measured
1 day after the procedure.
significantly immediately after transfusion but returned
to pretransfusion levels by the following day.
40
In fact, the PI was reduced
18
These data
suggest that the PI cannot be used as an indicator of fetal
anemia. However, new data suggest that MCA PSV evaluation is now the investigation of choice for noninvasive
diagnosis of fetal anemia due to Rh alloimmunization and
has practically replaced amniocentesis for amniotic fluid
in centers well trained in assessment of MCA PSV.
OD
450
Originally described in the 1990s, MCA Doppler PSV
has been studied extensively as a noninvasive method
of detecting fetal anemia. Mari and colleagues
lished MCA PSV above threshold of 1.5 multiples of the
median (MoMs) as an effective tool of prenatal diagnosis
of moderate to severe fetal anemia in patients with Rh
alloimmunization. Before use of MCA Doppler evaluation, serial amniocentesis to determine the bilirubin level
in amniotic fluid—by detecting change in optical density
at wavelengths of 450 nm—was the mainstay of management of alloimmunization in pregnancy. In a multicenter
prospective study, Oepkes et al
78
concluded that MCA
PSV Doppler evaluation was more sensitive and accurate
than amniotic fluid OD
anemia, with MCA PSV sensitivity, specificity, and accu-
in the diagnosis of severe fetal
450
racy of 88%, 82%, and 85%, respectively as compared with
76%, 77%, and 76%, respectively, for amniotic fluid OD
The MCA PSV is measured in the axial view of the
fetal head with pulsed Doppler gate over the vessel close
to its base at the circle of Willis for accurate measurement
( Figures 15–12 and 15–13 ). Three measurements should
be taken during the period of fetal apnea and absent fetal
77
estab-
450
.
PATHOLOGIC PREGNANCIES
Fetal Anemia
In neonatal polycythemia, partial plasma-exchange transfusion improves cerebral hemodynamics; the exchange
procedure results in significantly decreased hematocrit,
viscosity, and PI.
Vyas and colleagues
ity in the fetal MCA to be increased with anemia. The
blood flow velocity in red cell–isoimmunized pregnancies
was not related to fetal blood PO
18
74
found mean blood flow veloc-
, and the relation of
2
Figure 15–12. The technique for obtaining the correct positioning
of the middle cerebral artery (MCA) for Doppler velocity measurements.
Figure 15–13. The technique for obtaining the correct measurement.
The angle of insonation and the direction of the MCA is 0°. The measurements velocity and resistive indices are displayed on the right.
movement.
79 , 80
In pregnancies complicated by alloimmunization, MCA Doppler evaluation should be initiated in the
second trimester and performed weekly, and intrauterine
transfusion is indicated for severe anemia.
Elevated Placental Resistance
and Growth Retardation
The fetoplacental circulation is a low-resistance system
in which downstream flow continues throughout the cardiac cycle. The effects of elevated placental resistance on
diastolic blood flow in the main fetal arteries were studied by Fouron et al.
cally increased in exteriorized lambs by tightening a
string inserted into an exposed section of the umbilical
cord around the vein. Doppler flow-velocity waveforms
were measured over the cord through an acoustic bag.
Compression of the umbilical vein continued until retrograde diastolic flow was observed in the umbilical artery.
The patterns of diastolic flow observed after compression were as follows: descending aorta and aortic arch, retrograde; ascending aorta, bidirectional; and cephalic aorta,
forward. These were quite different from their respective
baseline patterns. The appearance of reverse diastolic flow
in the umbilical artery
vascular resistance in the fetal circulatory network is no
longer at the placental but at the cerebral level, and, second, that preplacental blood with low oxygen content from
the descending aorta and pulmonary artery is being shifted
toward the brain.
Loss of end-diastolic velocities in the fetal aorta and/
or umbilical artery was observed by Arabin and collabora-
83
in 30 of 137 high-risk pregnancies, indicating a high
tors
downstream impedance. All the fetuses were growthretarded, and the observations of absent end-diastolic
velocities were made nearly 8 days before pathologic
cardiotocographic findings. In nine cases, the ratio of the
blood flow volume in the common carotid artery to that of
the fetal aorta could be determined. The values were significantly increased compared with values of undisturbed
81
Placental resistance was mechani-
82
indicates, first, that the lowest
Chapter 15 Fetal Cerebral Circulation
437
pregnancies, demonstrating a redistribution of fetal blood
flow in favor of the cerebral circulation.
Failure of the physiologic invasion of myometrial spiral arteries by cytotrophoblasts in the second trimester and
the development of acute atherosis are phenomena associated with higher vascular resistance of the fetoplacental
vasculature.
84
Animal experiments have suggested that fetal growth
retardation is associated with reduced umbilical and placental blood flow and increased distal resistance.
85 , 86
Under
experimental conditions in animal models during hypoxia,
the redistribution of cardiac output and increased peripheral vascular resistance, with the aim of maintaining cerebral blood flow, resulted in the “brain-sparing” effect.
45 , 87
This phenomenon (see Figures 15–2 and 15–3 ) has been
suggested as the pathophysiologic mechanism for asymmetrical growth retardation in the human fetus and is
characterized by relative sparing of the brain with respect
to body weight. This reflex of centralization of the fetal circulation has already been established in fetal hypoxia.
31 , 88
Maximum reduction in PI was found when the fetal PO
was 2 to 4 standard deviations below the normal mean for
gestation. When the oxygen deficit was greater, there was
a tendency for the PI to rise, and this presumably reflected
the development of brain edema.
31
Compensatory redistribution is regulated by more than one mechanism; hypoxemia, alone or with hypercapnia, is responsible for cerebral
vascular responses.
89
In growth-retarded pregnancies, pulsatility in all of the
major intracranial arteries was significantly reduced compared with normal pregnancy, suggesting participation in
a brain-sparing effect in the presence of chronic fetal hypo
15 , 17 , 21 , 29 , 31 , 43 , 68 , 69 , 90 – 100
xia.
to be associated with poor obstetric outcome (ie, fetal
death and severe growth retardation).
Antenatally raised ratios were found
101
Therefore, the
brain-sparing effect is suggested as a mechanism to prevent fetal brain hypoxia, rather than as a sign of impending
brain damage.
Several studies have proposed Doppler criteria involving intracranial vessels to predict small-for- gestational-age
(SGA) neonates. We analyzed published data concerning
these criteria, for which sensitivity and specificity could be
determined.
102
The predictive values were computed using
Bayes theorem, based on an SGA prevalence rate of 10%.
Intracranial vessels had positive predictive values ranging
between 49% and 66%. The use of a lower prevalence rate
in Bayes formula would decrease the positive predictive
value of all parameters.
Conflicting findings preclude the clinical use of cerebral Doppler alone as a predictor of growth retardation.
For example, McCown and Duggan
103
found in 28 SGA
fetuses a highly significant association between an abnormal ICA waveform and a poor outcome; this was particularly pronounced at a gestational age of less than 34 weeks,
when the sensitivity, specificity, and predictive values were
all 100%. On the other hand, in a study of 44 cases of intrauterine growth retardation (IUGR) with eight perinatal
deaths, Wladimiroff and colleagues
100
found no correlation
between the indicators of fetal well-being (ie, Apgar score
at 1 min, fetal heart rate [FHR] patterns, and umbilical
arterial pH) and the ICA PI. This group
24
considered the
2
438
Chapter 15 Fetal Cerebral Circulation
end velocities in the ACA and MCA to be the most sensitive parameters discriminating between SGA fetuses and
controls but found the umbilical artery PI to be the best
indicator for the SGA fetuses.
Maternal hyperoxygenation has been suggested for
treatment of growth-retarded and hypoxic fetuses.
No effect was observed on placental RIs, but flow waveforms were modified in cerebral arteries.
106
Such a positive
104 , 105
response was found to be a good prognostic factor, in contrast to the poor prognosis associated with a negative test
response, which may indicate gross placental failure such
that fetal PO 2 cannot be improved.
107 , 108
Twin Discordance
The value of Doppler waveform analysis in the surveillance
of twin fetuses was assessed by us in a prospective longitudinal study.
umbilical artery gave an overall sensitivity in prediction of
an SGS fetus of 58% and a positive predictive value of 71%.
These data were not as sensitive and specific as our earlier
data.
of growth retardation by a mean interval of 3.7 weeks and
demonstrated greater specificity and sensitivity. A combination of these parameters improved sensitivity to 84% and
may complement real-time ultrasonography for the early
diagnosis of abnormal growth in twin pregnancies. Rizzo
et al
according to the underlying mechanism of growth defect.
Gaziano and colleagues
flow distribution in diamniotic monochorionic compared
with dizygotic (diamniotic dichorionic) twins. They found
that diamniotic monochorionic twins from the lowerbirth-weight group more often show blood flow redistribution compared with dizygotic twins of similar low birth
weight. Placental vascular connections and the attendant
hemodynamic changes in this group probably account for
this difference. Brain sparing events occurred commonly
without clinical twin transfusion syndrome.
changes in cerebral vessels of seven monochorionic
twins with twin-to-twin transfusion syndrome (TTTS).
These were compared with 8 monochorionic pairs and 11
dichorionic twin pairs. They found significant changes in
Doppler flow velocity and indices, which suggest instability
of cerebral blood flow with episodes of “hyperperfusion”
in monochorionic twins with TTTS. Although interesting
and to some extent logical, these data need to be correlated
and applied to neonatal neurologic outcomes. The MCA
PSVs in uncomplicated twin pregnancies were found to be
comparable with published singleton norms with a median
intertwine MCA PSV difference of ∼5 cm/s.
in monochorionic diamniotic twins as a longitudinal study.
This group’s goal was to establish terms for calculating
conditional reference intervals appropriate for individual
serial measurements. Based on 824 observations in 100
fetuses, normative ranges of 15 to 37 weeks were comparable for those in singletons. Their conclusion was that
47
Measurements of indices from the ICA and
46
However, Doppler changes preceded US diagnosis
109
found different trends in Doppler serial recordings
110
studied fetal growth and blood
108
Degani et al
studied the Doppler flow velocity
109
The role of MCA PSVs was studied by Klaritsch et al
110
between 18 and 37 weeks, reference ranges of singletons
can be used to assess fetal anemia in monochorionic/
diamniotic pregnancies. Prior to 18 weeks, the application
of singleton references may lead to an increased number of
false-positive diagnoses of presumed fetal anemia in such
twin pregnancies.
Grazianno et al
111
studied Doppler velocimetry in twins
with low-birth-weight groups. They evaluated Doppler
velocimetry to determine redistribution of fetal blood flow
and correlated growth restriction in diamniotic-monochorionic and dizygotic twins. They concluded that diamniotic-monochorionic twins from the lower-birth-weight
groups more often showed blood flow redistribution
compared with dizygotic twins of similar birth weights.
Placental vascular connections and the attendant hemodynamic changes in fetuses of amniotic monochorionic
twins probably account for this difference. Brain-sparing
events occur commonly without clinical twin transfusion
syndrome in this group.
Ventriculomegaly and Increased Intracranial Pressure
In adults, the volume of blood, spinal fluid, and brain tissue in the cranium at any time must be relatively constant
(Monro-Kellie doctrine).
and the open skull sutures enable better adaptation to
increased intracranial volume. Hill and Volpe
104
During fetal life, the fontanelles
113
the ventriculomegaly to be a more critical factor than the
intracranial pressure in the pathogenesis of the impaired
flow in infantile hydrocephaly.
The effect of ventriculomegaly on cerebral pulsatile
flow was studied by us in four hydrocephalic fetuses.
PI in the ICA showed progressive elevation, proportional
to the developing ventriculomegaly.
Van den Wijngaard et al
115
presented data on nine
fetuses with bilateral symmetrical hydrocephaly and four
with unilateral hydrocephaly. An elevated ICA PI was demonstrated in five cases. The fetal outcome was poor: Only
one infant seemed to be developing normally at 1 year of
age. However, in contrast to reports on elevated PI, according to Kirkinen and colleagues,
116
blood flow patterns seem
to differ individually from case to case. Normal, increased,
and decreased velocity waveform indices could be measured. The discrepancies in results may be related to different pathophysiologic mechanisms of hydrocephaly.
Posterior fossa subdural hematoma was diagnosed
antenatally by Ben-Chetrit et al
119
in a fetus at 30 weeks’
gestation. Doppler studies of the MCA showed an abnormally high resistance pattern with reverse end-diastolic
flow, reflecting high intracranial pressure; associated quadriplegia was noted during US assessment. Color Doppler
energy imaging (power Doppler) may help in the diagnosis
of intracranial hemorrhage.
intraparenchymal hemorrhage
118
Another case of cerebral
119
allowed the authors to
analyze the evolution of cerebral Doppler abnormalities,
but the modifications in Doppler velocimetry could not be
predicted.
The underlying disorder and the presence of other mal-
formations rather than cerebral blood flow measurements
found
114
The
Chapter 15 Fetal Cerebral Circulation
439
are of greater prognostic value regarding brain damage in
fetuses with hydrocephaly.
Arteriovenous Malformations
A cerebral cystic structure in the median plane with turbulent flow pattern in the lesion and decreased cerebral vascular resistance is typical of an arteriovenous malformation
112 – 114
(AVM).
to cardiac failure and nonimmune hydrops fetalis
An aneurysm of the vein of Galen may lead
113 , 115
(see
Chapter 9 ). Fetuses without evidence of hydrocephaly or
signs of cardiac insufficiency were followed and treated
postnatally by embolization.
flow in the draining prosencephalic vein was measured in
two cases by Goelz and colleagues.
116 – 118
Very-high-volume blood
119
The huge shunting
of blood flow in this vein was associated with the development of severe encephalomalacia and progressive heart
failure of both fetuses.
PHARMACOLOGICAL ASPECTS
Various drugs administered during pregnancy are reported
to affect cerebral blood flow.
Ritodrin infusion for premature uterine contractions
was associated with significantly decreased waveform indices in the MCA and renal artery. There was no change in
the indices of the umbilical artery.
Magnesium supplementation during pregnancy, particularly in cases of preterm labor, was found to be associated with a decrease in vascular resistance, both in the
umbilical artery and in the fetal MCA.
Indomethacin for preterm labor or polyhydramnios
resulted in constriction of the ductus arteriosus in 11 of
13 fetuses within 48 hours of therapy.
manifested both ductal constriction and tricuspid insufficiency, the PI of the MCA decreased significantly.
another randomized controlled trial,
not significantly affect cerebral blood flow. If antenatal
indomethacin in the preterm fetus increases the risk of
intraventricular hemorrhage, it would appear to be by
another mechanism.
Prostaglandin E
induction cervical ripening was found to be associated
administered intracervically for pre-
2
with increased pulsatility in the cerebral artery.
Nifedipine therapy for preterm labor had no influence on Doppler criteria of either fetal or uteroplacental
circulation.
122
Betamethasone administration causes a transient but
considerable reduction in fetal body and breathing movements and in fetal heart rate variation. No significant
changes occurred in the PI of uterine arteries, umbilical arteries, fetal aorta and renal artery, and fetal cerebral arteries, suggesting that the change is not mediated
through fetal hypoxemia.
123
Nicotine injections induced vasoconstriction on the
umbilical and cerebral arteries of ovine fetuses and were
associated with poor perinatal outcome.
Extradural anesthesia (eg, with bupivacaine) had no
detrimental effects on the uteroplacental and fetal circu-
49
118
119
In the fetuses that
119
121
In
120
indomethacin did
124
lation in the uncomplicated pregnancy when maternal
hypotension was avoided with rapid prehydration.
125
Oxygen administration to the mother was followed
by an increase of maternal PO 2 , which raised the pressure
difference in PO
increased if it was below the normal range. Oxygen
across the placenta.
2
administration had no effect on placental RIs but modified the waveforms in cerebral arteries.
101 , 102
103
Fetal PO 2
Maternal
oxygenation results in velocity waveform changes that
suggest an increase in cerebral vascular resistance and
a redistribution of blood from the brain to the vascular beds supplied by the ascending aorta.
104 , 105
Absent
or reversed end-diastolic velocity in the aortic isthmus
appears to be an early sign of blood redistribution in SGA
126
fetuses.
Carbon dioxide is also an important determinant of
cerebral blood flow. Inhalation of a prepared gas mixture with 2% to 3% carbon dioxide or increased PCO
patients undergoing controlled hyperventilation selectively caused a decrease in resistance in the fetal cerebral
circulation.
127 , 128
Both maternal and fetal cerebral vascular resistances were decreased by 30% nitrous oxide inhalation.
2
in
129
No adverse effects to the mother or fetus have been
demonstrated in clinical practice. However, preterm
fetuses are susceptible to intracranial hemorrhage, and the
cerebral hyperemia by nitrous oxide might increase the risk
of hemorrhage in these fetuses. From animal experiments
it is known that nitric oxide (NO) influences cerebral vascular tone both in the normal fetus and in the hypoxemic
130
Prostaglandins are important in facilitating the full
fetus.
expression of NO-induced vasodilation.
FETAL DISTRESS
The significant alterations in cerebral flow velocity and PI
in fetal hypoxemia and acidemia suggest the use of Doppler
criteria to detect imminent fetal distress in complicated
pregnancies. Combinations of Doppler parameters from
various vessels may be used:
1. The cerebroumbilical Doppler ratio (the ratio
between the PI of the MCA and the PI of the umbilical artery) is usually constant during the last 10
weeks of gestation.
was found to provide a better predictor for adverse
perinatal outcome than the PI of either artery alone.
The predictive value of the ratio in diagnosing SGA
newborns was 70%, compared with 54.4% for the
MCA and 65.5% for the umbilical artery.
2. Serial measurement of mean velocity of the fetal
descending thoracic aorta is the best fetal parameter identifying prolonged pregnancy at increased
risk for perinatal complications,
ratio of the fetal common carotid artery to the fetal
descending thoracic aorta had the highest predictive
capacity for the SGA pregnancy complicated by fetal
distress.
84
131
Using a single cut-off value, it
132
but the velocity