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Doppler Ultrasound Diagnosis in Preeclampsia, Eclampsia, and HELLP Syndrome
2
Hypertension
Brain
Gene­ralized­vaso­spasm
Fig. 10.1 The effects of vasospasm on various organs and development of symptoms.
viscosity, resulting in reduced perfusion. At the same time colloid osmotic pressure and the plasticity of the erythrocytes decrease.
Our own research showed that in women with pree­clampsia uterine and renal vascular resistance was in­creased. In order to determine if this increase in re­sistance also affected other maternal vessels, we addi­tionally examined the thyroid vessels. In these vessels there was no difference in perfusion between women whose pregnancy was normal, and those who suffered from preeclampsia, suggesting that the increase in re­sistance in the uterine and renal vascular beds must be of local origin. The reduction in perfusion in our pree­clamptic population was more marked in the kidneys than in the uterus.
Another attempt to explain the pathogenesis of preeclampsia was by abnormal immune processes. However, despite an increase in antibody formation in preeclamptic women so far no unequivocal evidence has shown this process to be causative in the clinical
Placenta
Kidney
Liver
Retina
Headache, seizures
Placental abruption, high infantile mortality
Oliguria, acute renal failure
Jaundice, acute hepatic failure
Double vision, amaurosis
picture of preeclampsia.
The primary symptom of preeclampsia is a rise in blood pressure in the course of pregnancy. The course of preeclampsia is monitored by following blood pres­sure and edema, as well as total protein and uric acid. Other available options include quantitative monitor­ing of albuminuria, ultrasonic monitoring of the fetus, and cardiotocography. Doppler ultrasound can provide important information concerning fetal condition in clinical picture.
Changes in the placental vascular bed can be demon­strated by tissue examination in patients with pree­clampsia and are relatively common. In such cases changes in the maternal vessels supplying the placenta may be demonstrated by Doppler ultrasound. Such Doppler sonographic changes can at times be demon­strated long before clinical symptoms appear, making Doppler ultrasound a future screening tool for pree­clampsia (cf. placental bed on the maternal side do not necessarily signify anomalies on the fetal side. In this respect the placenta has an enormous compensatory capacity.
As is to be expected, elevated blood pressures in the mother without placental changes are accompanied by normal flow profiles in the fetal and fetoplacental ves­sels.
There are altogether three indications for using Dop­pler ultrasound in diagnosis:
1. To anticipate or screen for the risk of preeclampsia by examining the uteroplacental vessels in the first or second trimester.
2. To confirm a diagnosis of preeclampsia in the sec­ond half of pregnancy by finding changes charac­teristic of preeclampsia in the uteroplacental bed, such as a notch or corresponding increases in re­sistance, correlating with a poorly developed placental vascular bed.
3. Evaluation of the fetal or fetoplacental vessels to ex­clude any risk to the fetus. The examination deter­mines how the fetus is coping with the changes re­sulting from the preeclampsia.
Chapter
9, p.). However, changes in the
104
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Evaluating the Risk of Preeclampsia in the First and Second Trimesters

Evaluating the Risk of Preeclampsia in the First and Second Trimesters—Examining the Uteroplacental Arteries

A significantly increased pregnancy risk results from failure of the adaptations needed to cope with the in­creased perfusion demand of the uteroplacentofetal unit.
At the onset of the second trimester a physiological
vasodilatation—probably the result of NO—leads to a demonstrable rise in diastolic flow rates in the utero­placentalaa. At theend of the26th week ofpregnancy at the latest this leads to the disappearance of the late sys­tolicnotch in the waveformof these aa. (Campbell 1993, Fleischer et al. 1986). These physiological changes are designed to provide an adequate blood supply to the placenta in the third trimester and, if they fail to occur, the result is often preeclampsia, gestational hyperten­sion, or fetal growthrestriction (Brosens 1977, Campbell et al.1983, 1986, Cohen-Overbeek etal. 1985, Hackettet al. 1986). Vascular occlusion leads to the same result (Sheppard and Bonnar 1980). By means of placental bi­opsies Voigt and Becker (1992) were able to demon­strate a correspondingly close correlation between morphological changes in the placental vascular bed and the uteroplacental waveform.
Doppler Ultrasound Findings
A late systolic notch in the waveform af ter the 26th
week of pregnancy reflects pathological changes in the placenta. This notch is an expression of the increased peripheral resistance opposing the pulse wave
generated by the ejection phase of the cardiac cycle. Such an increase in resistance, which is the result of va­soconstriction, canonly be generated because too many blood vessels, for this gestational age, are still sur­rounded by a muscular layer. By contrast, in a normal pregnancy blood vessels without muscle fibers are the preponderant vessels at the end of the 26th week of ge­station at the latest. This reduces the peripheral re­sistance and leads to the disappearance of the notch. CalculatingDoppler indices such as the pulsatility index (PI), resistance index (RI), or ratio of systolic peak to end-diastole(A/B ratio) is of no great value indetermin­ing pathological changes in the first half of pregnancy.
Thus, a postsystolic notch in the uteroplacental ves­sels is abnormal in the second half of pregnancy. As notedabove, it probablyrepresents theresult of a defec­tive trophoblast invasion during placentation in the first half of pregnancy. Campbell et al. (1983) con­sidered the notch to be the characteristicDoppler sono-
graphiccorrelate of preeclampsia. Fleischeret al. (1986) considered the notch, when accompanied by hyperten­sion, highly associated with dystocia and prematurity,
with a sensitivity of 83% and a specificity of 95%. Thus,
according to Gonser and Vetter (1995) this characteris­tic dual-phase notch is a better indicator of hyperten­sive complications of pregnancy than, for instance, creatinineclearance or plasma uric acid level.Kofinas et al. (1989) were able to demonstrate that the incidence of preeclampsia or intrauterine growth restriction (IUGR) was greater with unilateral implantation of the placenta than with central implantation. Gonser et al. (1993) made the complementary discovery that in the case of a unilateral placenta the findings from the uterine aa. on the contralateral side correlated signifi­cantly with the clinical and metabolic condition of the newborn:Where a notchis found, theoutcome is signif­icantly worse than when this is absent. According to Thaler et al. (1992),when a notchis found, theincidence of cesarean section for abnormal cardiotocogram (CTG) is also increased. The subjects in all the studies cited so far were from a high-risk population. Steel et al. (1990), on the other hand, studied the possibility of including Doppler sonography of the uteroplacental vessels in a screening protocol for preeclampsia, by examining the uterine aa. of a population of healthy pregnant women during the 18th and 24th weeks of pregnancy. In cases where the Doppler findings were abnormal in both ex­aminations (i. e., they showed a notch), the risk for sub­sequent hypertensive complications of pregnancy in­creased significantly. Steel et al. found the risk for hy­pertension increased from 5% to 25 %, for preeclampsia from 1 % to 10%, and for fetal hypotrophy from 7 % to 27%. Harrington et al. (1991) in a comparable screening study calculated a sensitivity of 76% at a specificity of 96% for the subsequent development of preeclampsia after corresponding changes in the uterine vessels. It follows from these studies that a Doppler screening ex­amination of the uteroplacental vessels may detect an impending preeclampsia.
Since it is possible to determine the risk of a ge­stational hypertensive disorder, the question naturally arises of how to prevent its development. The adminis­tration of low-dose acetylsalicylic acid (ASA) has been hypothesized to have a positive influence on the course of the disease. McParland et al. (1990) administered prophylactic aspirin to pregnant subjects (excluding nulliparae) with abnormal Doppler findings on screen­ing during the 18th week of pregnancy and a controlex­amination at 24th weeks. The dosage was 75 mg ASA a day vs. placebo. The results showed that administering ASA reduced the frequency of hypertensive complica­tions of pregnancy and of preeclampsia significantly. The rate of cesarean sections for these conditions was alsoreduced. There wasno changein bleeding tendency due to the medication, and no other side effects due to the low-dose ASA were listed.
Obstetric Applications of Doppler Ultrasound
105
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Doppler Ultrasound Diagnosis in Preeclampsia, Eclampsia, and HELLP Syndrome
Confirming a Diagnosis of Preeclampsia in the Second Half of Pregnancy—Demon­strating Characteristic Doppler Sonographic Changes of Preeclampsia in the Utero-
placental Vessels
2
Doppler examination of the uteroplacental aa. during the first half of pregnancy is used to determine the risk for the subsequent development of preeclampsia. The question in the second half of pregnancy is whether examining the uteroplacental vessels when clinical symptoms of preeclampsia are already present would be of any use. In this case Doppler examination will most often show a notch, since the above-mentioned changes in the uterine aa. are presumably present. However, the finding is not as significant as in the first half of pregnancy. If a notch can be demonstrated, it is likely that the gestational hypertension or preeclam­psia was caused by the sequence of events following a defective trophoblast invasion. If the notch is absent, such a causal connection is not confirmed for the in­dividual case, but there is no change in clinical man­agement: As soon as clinical signs of preeclampsia are
present, management depends on the maternal and fetal condition, not on the Doppler findings in the uterine aa.
Finding a notch therefore allows a pathophysiologi­cal sequence to be postulated, perhaps satisfying diag­nostic curiosity. However, such a finding does not change the obstetric management. It follows that this diagnostic procedure is of secondary importance in the second half of pregnancy.
Doppler Sonographic Findings
The finding to be noted in the second half of pregnancy is the notch described above. To be significant we rec­ommend a threshold value of the 90th to 95th percen­tile of the Doppler indices.

Evidence for or Exclusion of Fetal Risk—Evaluating the Fetal or Fetoplacental Vessels

The task is to distinguish between chronic changes caused by preeclampsia, or acute problems occurring without warning. The former can be demonstrated by Doppler ultrasound in the fetal vessels when they lead to poor blood supply in the fetus; however, an acute rise in maternal blood pressure can lead to fetal dis­tress, which may elicit changes in the CTG, but does not appear in the Doppler sonogram. In rapid changes of this kind with placental insufficiency, fetal flow pat­terns may be unchanged, because the infant has had no time to respond.
By contrast, when a long-term deficiency in the placental supply—caused by the deficient trophoblast invasion noted above—results in fetal growth restric­tion, decompensation of the placental supply may re­sult in abnormal Doppler findings in the umbilical aa. or fetal vessels.
The prime consideration is that abnormal flow pat­terns on the maternal side do not necessarily cause ab-
Fig.
normal flow patterns on the fetal side ( instance, the experience in our clinical practice is that not all infants born to women showing symptoms of preeclampsia are delivered growth restricted or pre­maturely.
10.2). For
Doppler Sonographic Findings
While vascular changes specific to preeclampsia such as a notch may be found in the uteroplacental vessels on the maternal side, no changes in the waveforms of the fetus are characteristic of preeclampsia. Risk to the fetus is shown by an increased resistance, i. e., in the first instance by reduction in diastole in the umbilical aa. and the fetal aorta.
Reductions in diastolic flow (e.g., RI above the 90th to 95th percentile) in the fetal aorta or the umbilical aa. are considered to be abnormal Doppler patterns.
Absent or reversed end-diastolic flow (ARED) in these vessels is the most important alarm signal. The centralization of the fetal circulation, i. e., increase in the peripheral resistance and decrease in the re­sistance of the central vessels is a sign of increased risk
F
igure
to the fetus. normal and abnormal flow profiles in the fetal and ma­ternal vessels.
There is some promise for the future that examina­tion of fetal v.’s (ductus venosus, vena cava, hepatic v.’s, and umbilical v.) may provide additional parameters for the detection of fetal risk (cf. Chapter18, p. 161).
10.3 provides an overview of the
106
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Evidence for or Exclusion of Fetal Risk—Evaluating the Fetal or Fetoplacental Vessels
Uterine a.
(normal finding)
Umbilical a.
(normal finding)
Fig. 10.2 An abnormal flow profile in the uterine a. should not automatically lead to the conclusion that the flow profile of the
Uterine a.
(abnormal finding)
Obstetric Applications of Doppler Ultrasound
Umbilical a.
(abnormal finding)
umbilical a. is abnormal. All combinations of abnormal and physiological flow profiles can occur.
Redistribution of Blood (Brain Sparing)
The concept of “brain sparing” ties the redistribution of cardiac output to the essential organs heart, adrenals, and brain at the expense of the rest of the body, such as the intestines, the skin, or the kidneys. The term “re­distribution” is more appropriate, since it carries fewer implications than “brain sparing.”
Redistribution is considered to be a fetal emergency adaptation, especially for respiratory function. In ani­mal experiments the effect can be elicited at will. Simi­larly, in human gestation an association can be found between an abnormal intrauterine blood gas analysis and redistribution.
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The term redistribution is generally used when Dop­pler sonography shows a change in the systolic/dias­tolic variability in the indicator vessels. The Doppler ultrasound indices used include the PI, RI, or the S/D ratio. With increased diastolic flow velocities the in­dices are lower in the favored organs, while in the re­maining vascular regions flows may slow or stop en­tirely or, in some cases, even reverse. With quantitative analysis, for example, when taking readings of abso­lute flow rates from specific vessels, an increase in flow rates in the selectively perfused organs can be clearly demonstrated.
Certain vessels are more accessible. Among these, the middle cerebral a., the descending aorta, and the
107
Doppler Ultrasound Diagnosis in Preeclampsia, Eclampsia, and HELLP Syndrome
2
a
c
b
d
108
e
g
Fig. 10.3 Compilation of physiological and pathological flow profiles in fetal and maternal vessels, especially in the third trimester.
a Uterine a., normal finding. b Uterine a., abnormal finding. c Aorta, normal finding.
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f
h
d Aorta, abnormal finding. e Umbilical a., normal finding. f Umbilical a., abnormal finding. g Middle cerebral a., normal finding. h Middle cerebral a., abnormal finding.

Summary

umbilical aa. are most often selected. The activity of the fetus must be taken into account, as it can in­fluence the Doppler readings from the middle cerebral a. When the fetus is active, diastolic flow velocities in­crease in relation to the systolic peak velocity, and ab­solute velocities also increase.
The slogan “heart sparing” has been used in corre­sponding examinations of the coronary aa.. In addition to the heart and the brain, the same effect could also be found in a third selectively perfused organ, the adrenal
gland. Whether examination of still other organs would expand our understanding is not clear.
The development of Doppler sonographic changes in opposite directions of the umbilical a. and the middle cerebral a., i. e., reduced diastolic flow rates in the umbilical a. and increased flow rates in the middle cerebral a., is of great practical importance in daily practice, independent of more refined pathophysio­logical measurements.
Summary
By examining the maternal vessels using Doppler ul­trasound it is possible to determine the risk of compli­cations developing in the course of a pregnancy long before clinical signs of preeclampsia appear, so that therapeutic measures may be undertaken early. Moreover, clinical symptoms arising in the third trimester can be shown by examination of the utero-
Redistribution is not a static process, but rather a compensation mechanism that changes with increas­ing disruption in the supply. With continuing decom­pensation the initially increased flow velocity in the middle cerebral a. decreases—a pseudonormalization of blood flow. For this reason the interpretation of Dop­pler readings without knowledge of their development over time or of related findings is insufficient. Ulti­mately diastolic flow may be absent or even reverse. This state has been associated among other pathology with cerebral edema.
It should be noted that the same effect may be eli­cited by increased pressure on the fetal head by the transducer. For this reason it is essential to check the stability and consistency of the findings and to relate them to other results before evaluating their clinical impact.
Obstetric Applications of Doppler Ultrasound
placental vessels to be caused by a defective tropho­blast invasion. However, the decisive use of Doppler sonographic findings in the third trimester is that it has a bearing on the timing of labor, thus reducing per­inatal mortality, i.e., it allows the obstetric attendant to select the optimal management.
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109
2
110
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11 Doppler Ultrasound in the Diagnosis of Fetal Anomalies

It is axiomatic that the initial diagnosis of fetal anoma­lies is made by conventional gray-scale B-mode sono-
graphy. However, Doppler ultrasound—especially color-coded blood flow diagnosis—increasingly allows the diagnosis to b e refined and more precisely de­lineated. Thus, whereas the detection of an anomaly depends on the experience of the examiner and the resolution of the B-mode image, the use of color Dop­pler ultrasound is highly advantageous in further ex­ploring organ function and differential diagnosis. This is accepted unanimously for fetal echocardiography. However, even a simple example will demonstrate the importance of color Doppler ultrasound in the diagno­sis of malformations: The differential diagnosis be­tween an intracerebral cyst and an aneurysm can be made with certainty only using color-coded Doppler ultrasound, since an aneurysm will be outlined in color, while a cyst remains colorless.
But even the demonstration of a normal vascular tree or pathological changes in it can clarify fetal anomalies. For instance, the demonstration by color Doppler of the absence of a renal a. can prove renal agenesis.
However, the precondition for the diagnosis of fetal anomalies is the correct setting of the instrument. For the display of venous flows, the setting must be adapted to their slow range of flow velocities, i.e., a
low pulse repetition frequency (PRF) must be selected. By contrast, the faster arterial flow rates can only be displayed accurately with higher PRFs.
Since, as stated above, the diagnosis of fetal anoma­lies depends primarily on a high-resolution B-mode image, only those fetal anomalies in various organ sys­tems are described in the following for which diagno­sis is facilitated by using color Doppler sonography. They are listed in Table
Tabelle 11.1 Diagnoses and further differentiation of fetal malformations that can be markedly facilitated by color Dop­pler ultrasound.
Region of body Fetal malformationKörperregion
Central nervous system, head, neck
Lung Hypoplasia of the lung (?),
Heart All cardiac anomalies Gastrointestinal tract Omphalocele, gastroschisis Urogenital system Renal malformations Skeleton Sacrococcygeal teratomata Other anomalies Placenta, hydrops fetalis,
11.1.
Arachnoid cysts, porencephalic cysts, intracranial neoplasms, hydrocephalus, tumors of the neck, fetal goiters, hemangiomata
diaphragmatic herniae, hemangio­mata
anhydramnios, anomalies of the umbilical cord
Obstetric Applications of Doppler Ultrasound

Anomalies in the Region of the Head and Neck

Examination of this region of the body by color Dop­pler is most profitable for anomalies of the fetal brain and soft-tissue tumors of the neck.
A normal color Doppler display of the blood supply
at the base of the skull is shown in
display showing intracerebral cysts might be of an
A actual cystic space such as an arachnoidal cyst, a ventricular hydrocephalic dilatation, cystic brain anomalies as in holoprosencephaly, choroid plexus cysts, or aneurysms of the vein of Galen. Naturally only aneurysms will show blood flow inside the cyst, while other anomalies by their nature do not (
Additionally, the spectral Doppler feature of Doppler ultrasound examination of the intracerebral aa., espe-
Figure 11.1.
Fig. 11.2a−c).
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111
Fig. 11.1 Display of the normal vascular supply at the base of
the skull. Circle of Willis with middle cerebral a.
Doppler Ultrasound in the Diagnosis of Fetal Anomalies
2
a
c
cially the middle cerebral a., permits conclusions to be drawn about intracerebral pressure.
The thickness of the cerebral cortical mantle in hy-
Fig.
drocephalus ( nosis for cognitive development. Perhaps in the future the degree of intracranial pressure, measured by Dop­pler sonography, may provide such an indication (Fig. 11.3b).
Postpartum changes in blood flow velocity in rela­tion to the degree of ventricular dilatation in hydro­cephalus may be divided into three stages:
11.3a) is not an indicator of the prog-
b
Fig. 11.2a Fetal brain with several cysts, which on color Dop­pler are seen to be filled with blood, showing they are
aneurysms.
Fig. 11.2b, c Additional cuts display more aneurysms in the brain.
Stage 1: In the slowly developing so-called “low-pressure hy­drocephalus,” in which the ventricles are only mini­mally dilated, no significant changes can be found by Doppler ultrasound in the flow rates in the intracranial vessels. Stage 2: In moderately dilated ventricles increased diastolic blood flows may be found, and these may lead to a re­duced pulsatility index (PI). This phenomenon is inter­preted as increased perfusion and a protective mecha­nism for cerebral tissue (brain sparing).
112
Fig. 11.3a Fetal hydrocephalus in the 33rd week of gestation. Fig. 11.3b Physiologically there should be diastolic forward
flow in the 32nd week of gestation. The middle cerebral a. in this infant exhibits zero diastolic flow, which may indicate in­creased intracranial pressure.
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Anomalies of the Lung and Diaphragm

Stage 3: Rapidly progressive ventricular dilatation is marked by a significant reduction in diastolic amplitude. In espe­cially severe cases blood flow may even be reversed (Fig. 11.4).The result isa raised PI.Such a findingis an in­dicator of impending ischemic cerebral tissue damage.
A derivation of this postpartum procedure is the use
of Doppler ultrasound ante partum.
In a fairly large number of cases of hydrocephalus
Voigt and his co-workers (Voigt et al. 1995) demon-
Fig. 11.4 Display of reverse diastolic flow in the middle cere­bral a., suggesting very high intracranial pressure.
strated that increasing ventricular dilatation led to in­creased resistance in cerebral blood flow, with con­sequentimpairment of perfusion. In this waythe reduc­tion in the cortical mantle was associated with an in­crease in intracerebral pressure. The authors point out that Doppler ultrasound is the ideal means of determin­ing the correct time for delivery in order to prevent damage to the fetal brain by excessive pressure.
Figure
11.5 shows the relationship betweenperfusion pressure and increased intracerebral pressure.
P
(mmHg)
P
(mmHg)
V
BP
ICP
BP
ICP
cm/s
t (s) t (s)
V
cm/s
t (s)t (s)
Obstetric Applications of Doppler Ultrasound
Fig. 11.5 Association between perfusion pressure (PP) and
flow profile in the cerebral arteries (PP = BP−ICP). The left side shows the relation between blood pressure (BP), which is con­sidered constant, and increasing intracranial pressure (ICP). The right shows the corresponding Doppler spectra that might be expected theoretically. As ICP increases, PP decreases with a consequent decrease in diastolic flow. Once ICP reaches end-di­astolic pressure, no more forward flow can be detected. If ICP exceeds BP during diastole, the result is end-diastolic flow rever­sal (after Voigt et al 1995).
Anomalies of the Lung and Diaphragm
Hypoplasia of the lung cannot be diagnosed or eval­uated with absolute certainty by B-mode imaging.
There is some hope that in the future displaying the perfusion of the lung may facilitate diagnosis by allow­ing conclusions about pulmonary function to be drawn from the vascular tree.
Diaphragmatic hernia is always associated with an anomaly and displacement of the lung, making the evaluation of pulmonary function of great prognostic
P
(mmHg)
P
(mmHg)
V
BP ICP
cm/s
t (s) t (s)
V
ICP
BP
cm/s
t (s)t (s)
importance. In this, color-coded Doppler ultrasound could provide significant assistance.
Cystic areas in the fetal lungs that lie very close to the heart may be delimited from the latter because they are not fille d with blood.
Malformations of the lungs, like hemangiomata, may be assigned to definite areas by their perfusion.
113
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