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Physiology of Doppler Flow in Maternal Vessels during Pregnancy
without an increased difference between the two sides), we in­terpreted this as a severe form of abnormal uterine perfusion. These groups (III, V,and VI) had severefetal circulatory changes that affected all the fetal vessels, suggesting that the presence of two or three abnormal perfusion parametersleads to serious fetal compromise
7
. For this reason, Doppler velocimetry of both uterine arteries is recommended for the clinical assess­ment of uterine perfusion.
Postsystolic notch. A postsystolic notch in uteroplacental waveforms during the second half of pregnancy indicates an abnormal pulse-wave reflection in the spiral arteries—pre­sumably a result of deficient trophoblastic invasion during placentation. The presence of a postsystolic notch is the Dopp­ler sign of preeclampsia
3
and has a very strong association with intrauterine growth retardation.The notch should no longer be detectable after 24 weeks’ gestation; otherwise there is a 70 % likelihood of a pregnancy complication with hypertension
Uterine Perfusion on Medication or after Uterine Manipulation
13
Mechanisms of action of intravenous beta-mimetics. The in­creased perfusion rate of the gravid uterus in response to in­travenously administered beta-mimetics is based on two mechanisms: an increase in cardiac output and a lowering of peripheral vascular resistance. Since we also observed a fall in the pulsatility index, it is reasonable to assume that the more important mechanism is peripheral vasodilation. The calcu­lated pulsatility index is less affected than the S/D ratio by an increased diastolic blood flow velocity caused by the increase in cardiac output.
No effect of amniocentesis, cervical cerclage, or oral beta-mi­metics. In our study population, which was homogeneous for
gestational age, we found that amniocentesis, cervical cer­clage, and orally administered beta-mimetics produced no change in uterine perfusion that was measurable by vaginal sonography. The intravenous administration of beta-mimetics led to a fall in the S/D ratio and pulsatility index.
Our findings confirm the clinical experience that none of the foregoing procedures hampers blood flow to the pregnant uterus and that the intravenous administration of beta-mimet­ics even appears to improve it.
It is interesting to note that nifedipine administration pro-
duces similar
results
sponse to indomethacin
29
, but this effect has not been seen in re-
therapy
21
.
Doppler Flowmetry of Maternal Vessels as a Screening Test?
The Doppler flowmetry of maternal blood vessels is an impor­tant step in evaluating the blood flow of the fetomaternal
11, 3 2
unit trimester, the transvaginal pulsed Doppler velocimetry of both uterine arteries can also be recommended as a screening test at the end of the second trimester. Placentation is already complete by this time, so that the physiological processes of trophoblastic invasion will not produce false-positive findings (difference between the sides).
14
.
Sensitivity for lateral hypertension. When both uterine arteries are examined and the resistance indices are calculated, Dopp­ler velocimetry of the uterine arteries can be done as early as the 22nd week of gestation to screen for pregnancy complica­tions. In the study by Valensise et al. sensitivity of 50% for predicting later pregnancy-induced hy­pertension, 88% for preeclampsia, and 100% for intrauterine growth retardation.
Negative predictive value. Abnormal uterine artery waveforms can have clinical implications when detected as early as the 24th week of gestation. The negative predictive value of this method is impressive: with a normal finding, there is a 96 % likelihood that a pregnancy complication will not occur sufficient in these cases to schedule follow-up examinations at about four-week intervals. It should be emphasized, however, that not all pregnancy complications can be predicted and di­agnosed by Doppler flowmetry. It has been shown that this method is most rewarding in cases of pregnancy-induced hy­pertension or intrauterine growth retardation, and therefore the test should be performed in patients who are considered from their history to be at risk.
False-positive results. On the other hand, there is a possibility of false-positive test results, and the measurements cannot al­ways be interpreted with complete certainty. As a result, uterine artery velocimetry cannot presently be recommended as a general screening test for all pregnancies
. Besides its use for risk assessment in the first
39
, this screening test had a
33
.Itis
2, 17
.
122

Summary

Doppler velocimetry of maternal vessels is one tool that is used for evaluating the perfusion of the fetomaternal unit. The most rewarding vessels are those that are directly or indirectly re­sponsible for sustaining the pregnancy. Abnormalities in the waveforms of major uterine vessels show a strong correlation with the presence or subsequent development of fetal growth retardation and preeclampsia. Flowmetry of the arcuate arter­ies can sometimes lead to false results in patients with exten­sive placental infarcts and in smokers because the examination
is confined to a circumscribed, terminal portion of the vascular bed.
Doppler velocimetry in a normal early pregnancy demon­strates high systolic and low diastolic flow velocities combined with a high S/D ratio and a high pulsatility index. The diastolic flow velocity increases with advancing gestation, leading to a decline in the S/D ratio and pulsatility index.
References
References
1 Arabin B: Die Bedeutung von Perzentilenwerten utero-plazentarer
und fetaler Blutflußparameterfür die klinische Praxis. Ultraschall Klin. Prax. Suppl. 1 (1987) 51
2 Bewley S, Cooper D, Campbell S: Doppler investigationof uteroplacen-
tal blood flow resistance in the second trimester: a screening study for pre-eclampsia and intrauterine growth retardation. Brit. J. Obstet. Gy­necol. 98 (1991) 871–879
3 Campbell S, Griffin DR, Pearce JM, Wilson K, Teague MJ: New Doppler
technique for assessing uteroplacental blood flow. Lancet 1 (1983) 675–677
4 Campbell S, Pearce JM, Hackett G, Cohen-Overbeek T, Hernandez C:
Qualitative assessment of uteroplacental blood flow: early screening test for high-risk pregnancies. Obstet. Gynecol. 68 (1986) 649–653
5 Chaoui R, Hoffmann H, Bollmann R, Halle H, Zienert A, Metzner A: Er-
fassung der uteroplazentaren Durchblutung ungestörter Schwanger­schaften mittels gepulstem Doppler. Ultraschall. Zentralbl. Gynäkol. 112 (1990) 11–18
6 Deutinger J, Rudelstorfer R, Bernaschek G: Vaginosonographic
velocimetry of both main uterine arteries by visual vessel recognition and pulsed Doppler method during pregnancy. Amer. J. Obstet. Gyne­col. 159 (1988) 1072–1076
7 Deutinger J: Vaginosonographische gepulste Doppler-Strömungsmes-
sungen in Gefäßen des kleinen Beckens. Enke, Stuttgart 1990
8 Deutinger J, RudelstorferR, Bernaschek G: Vaginosonographic Doppler
velocimetry in both uterine arteries: elevated left-right differences and relationship to fetal haemodynamics and outcome. Early Hum. Develop. 25 (1991) 187–196
9 Deutinger J, Rudelstorfer R, Pattermann A, Bernaschek G: Vaginosono-
graphic velocimetry in uterine arteries before and after administration of beta-mimetics. Brit. J. Obstet. Gynaecol. 99 (1992) 417–421
10 Dickey RP, Hower JF: Ultrasonographic features of uterine blood flow
during the first 16 weeks of pregnancy. Hum. Reprod. 10 (1995) 2448– 2452
11 Fendel H, Fendel M, Warnking R: Fehlermöglichkeiten der gepulsten
Dopplermethode zur Blutflußmessung am Feten. Z. Geburtsh. Perinat. 187 (1983) 83–87
12 Fendel H, Fendel M, Jörn H, Funk A, Docker B, Meyer W: Doppler-Score
zur Beurteilung des perinatalen Risikos. Ultraschall Klin. Prax. 5 (1990) 68–73
13 Fischer RL, Kuhlman KA, Depp R, Wapner RJ: Doppler evaluation of
umbilical and uterine-arcuatearteries in the postdates pregnancy.Ob­stet. Gynecol. 78 (1991) 363–368
14 Fleischer A, Schulman H, Farmakides G: Uterine artery Doppler
velocimetry in pregnant women with hypertension. Amer. J. Obstet. Gynecol. 154 (1996) 806–813
15 Fuller EO, Galletti PM, Takeuchi T: Major and collateral components of
blood flow to pregnant sheep uterus. Amer. J. Physiol. 229 (1973) 279– 285
16 Hanretty KP, Whittle M: Doppler uteroplacental waveforms in preg-
nancy induced hypertension: A re-appraisal. Lancet 1 (1988) 850–852
17 Jacobson S, Imhof R, Manning N et al.: The value of Doppler assessment
of the uteroplacental circulation in predicting preeclampsia or in­trauterine growth retardation. Amer. J. Obstet. Gynecol. 162 (1990) 110–114
18 Jauniaux E, Zaidi J, Jurkovic D, Campbell S, Hustin J: Comparison of
color Doppler features and pathological findings in complicated early pregnancy. Hum. Reprod. 9 (1994) 2432–2437
19 Kurjak A, Predanic M, Kupesic-Urek S: Transvaginal color Doppler in
the assessment of placental blood flow. Eur. J. Obstet. Gynecol. Reprod. Biol. 49 (1993) 29–32
20 Kurjak A, Zalud I, Predanic M, Kupesic S: Transvaginalcolor and pulsed
Doppler study of uterine blood flow in the first and early second trimesters of pregnancy: normal versus abnormal. J. Ultrasound Med. 13 (1994) 43–47
21 Mari G, Kirshon B, Wassersturm N, Moise KJ, Deter RL: Uterine blood
flow velocity waveforms in pregnant women during indomethacin therapy. Obstet. Gynecol. 76 (1990) 33–36
22 Matijevic R, Meekins JW, WalkinshawSA, Neilson JP, McFadyen IR: Spi-
ral artery blood flow in the central and peripheral areas of the placen­tal bed in the second trimester. Obstet. Gynecol. 86 (1995) 289–292
23 McCallum WD, Williams CS, Nagel S, Daigle RE: Fetal blood flow veloc-
ity waveforms. Amer. J. Obstet. Gynecol. 132 (1978) 425–429
24 Merce LT, Barco MJ, Bau S: Color Doppler sonographic assessment of
placental circulation in the first trimester of normal pregnancy. J. Ul­trasound Med. 15 (1996) 135–142
25 Moll W, Nienartowicz A, Hes H, Lenz A: Blood flow regulation in the
uteroplacental arteries. Trophoblast Res. 3 (1988) 83–96
26 Oosterhof H, Wichers G, Fidler V, Aarnoudse JG: Blood viscosity and
uterine artery flow velocity waveforms in pregnancy: a longitudinal study. Placenta 14 (1993) 555–561
27 Olofson P, Laurini RN, Marsál K: A high uterine artery pulsatility index
reflects a defective development of placental bed spiral arteries in pregnancies complicated by hypertension and fetal growth retarda­tion. Eur. J. Obstet. Gynecol. Reprod. Biol. 49 (1993) 161–168
28 Palmer SK, Zamudio S, Coffin C: Quantitative estimation of human
uterine artery blood flow and pelvic blood flow redistribution in preg­nancy. Obstet. Gynecol. 80 (1992) 1000–1006
29 Pirhonen JK, Erkkola RU, Ekblad UU: Uterine and fetal flow velocity
waveforms in hypertensive pregnancy: the effect of a single dose of nifedipine. Obstet. Gynecol. 76 (1990) 37–41
30 Ruckhäberle KE, Faber R, Robel R, Viehweg B: Diagnostik und Therapie
gestörter Hämodynamik. Ein Beitrag zum Management bei Schwangerschaften mit drohender Frühgeburt. Z. Geburtsh. u. Perinat. 196 (1992) 152–158
31 Schulman H, Fleischer A, Stern W, Farmakides G, Jagani N, Blattner P:
Umbilical velocity wave ratios in human pregnancy. Amer. J. Obstet. Gynecol. 148 (1984) 985–990
32 Schulman H, Fleischer A, Farmakides G, Bracero L, Rochelson B, Grun-
feld L: Development of uterine artery compliance in pregnancy as de­tected by Doppler ultrasound. Amer. J. Obstet. Gynecol. 155 (1986) 1031–1036
33 Schulman H: The clinical implications of Doppler ultrasound analysis
of the uterine and umbilical arteries. Am. J. Obstet. Gynecol. 156 (1987) 889–893
34 Sohn C, Kesternich P, Fendel H: Der Einfluß der Körperposition auf die
uterine Durchblutung im 3.Schwangerschaftstrimenon. Ultraschall 10 (1989) 10–14
35 Sohn C, Stolz W: Untersuchung zur Entwicklung der Dopplerparame-
ter in fetalen und mütterlichen Gefäßen 10 Tage vor bis 10 Tage nach errechnetem Geburtstermin. Geburtsh. u. Frauenheilk. 54 (1994) 102– 107
36 Thaler I, Manor D, Itskovitz J et al.: Changes in uterine blood flow
during human pregnancy. Amer. J. Obstet. Gynecol. 162 (1990) 121– 125
37 Tonge HM, Wladimiroff JW, Noordam MJ, van Kooten C: A study on
fetal blood flow velocity waveforms in cases of intrauterine growth re­tardation. Obstet. Gynecol. 67 (1986) 851–855
38 Trudinger BJ, Giles WB, Cook CM: Uteroplacental blood flow velocity-
time waveforms in normal and complicated pregnancy. Brit. J. Obstet. Gynaecol. 92 (1985) 39–45
39 ValensiseH, Bezzeccheri V,Rizzo G, Tranquilli AL, Garzetti G, Romanini
C: Doppler velocimetry of the uterine artery as a screening test for ges­tational hypertension. Ultrasound Obstet. Gynecol. 3 (1993) 18–22
40 Wladimiroff JW, Tonge HM, Stewart PA: Doppler ultrasound of cere-
bral blood flow in the human fetus. Brit. J. Obstet. Gynaecol. 93 (1986) 471–475
Obstetric Ultrasound
123
Color Doppler Sonography of the Uterine Arteries in
14
Early Pregnancy to Screen for Preeclampsia and Uteroplacental Insufficiency
A. Funk

Applications of Color Doppler Sonography during Pregnancy

Placental insufficiency and preeclampsia in the third trimester.
Doppler sonography of the uterofetoplacental unit in the third trimester is part of the standard diagnostic workup of patients with suspected placental insufficiency and preeclampsia. At this late stage of gestation, however, it is possible only to con­firm the presence of a chronic perfusion def icit. The Doppler findings, along with B-mode findings and biophysical and bio­chemical tests, are helpful in assessing the degree of fetal com­promise and directing clinical management.
14
Early detection of decreased uterine perfusion. The efforts of modern me dicine are also aimed at early detection, clinical in­tervention, and prevention, and these goals have prompted the use of transvaginal ultrasound scanning to assess blood flow early in the pregnancy.
Changes in the spiral arteries. The central question is whether Doppler sonography is able to confirm the normal develop­ment of blood flow and also detect decreased blood flow during the first half of pregnancy. Another key issue is whether Doppler evidence of decreased uterine perfusion actually correlates with the development of pregnancy-induced hyper­tension (PIH) and intrauterine growth retardation.
Normally a massive increase of blood flow occurs during the first half of pregnancy, and this requires a morphological transformation of the spiral arteries as described by Brosens et
3
al.
. Trophoblastic cells invade and erode the musculoelastic
media of the spiral arteries, transforming the vessels into large,
saclike tubes with a funnel-like expansion at their junction with the intervillous space. These changes take place between the 14th and 20th weeks of menstrual age and are completed no later than the 24th week, even when maturation is delayed. The calibers of the spiral arteries are increased by a factor of 30, the arcuate arteries by a factor of 10, and the uterine arteries by a factor of 1.5–3
Blood circulation in the intervillous space. The blood flow changes that occur during the first trimester are more difficult to classify. Hustin and Shaaps logical, and morphological studies showing that intervillous blood circulation does not occur before the 12thweek of gesta­tion. This led them to conclude that there is no contact between the chorionic villi and maternal blood during the first trimester andthat theembr yo andplacenta areindependent ofthe mater­nalenvironment. Theydistinguished betweena periodin which implantation, organogenesis, and placentation occur and a sec­ond period that begins with active maternalblood flow through the intervillous space toward the end of the first trimester.
It is reasonable to conclude that uterine blood flow in the first trimester is controlled in part by the rising estrogen levels in the maternal serum. This can be inferred from the fact that cyclic changes in uterine blood flow correlate with the estradiol level in muscle cells of the uterine arteries have shown dilatation of the terminal segments of the uterine vessels prior to trophoblast invasion
2
.
7
performed hysteroscopic,radio-
4, 12
, that estrogen receptors have been identified
9
, and that animal studies
10
.
124

Technique of Transvaginal Doppler Sonography

Transducer placement. With the patient in the lithotomy posi-
tion, the ultrasound probe, sheathed in a condom and smeared with contact gel, is inserted into the vagina until it is in contact with the anterior fornix (anteflexed uterus) or posterior fornix (retroflexed uterus). An initial survey is carried out, and the probe is positioned in the lateral fornix so that it is in direct contact with the uterine attachment of the parametrium through the vaginal wall. The proximity to the target organs makes it possible to use transducer frequencies of 5 MHz or higher, which are excellent for blood flow studies.
Vascular anatomy. After arising from the internal iliac artery, each uterine artery, surrounded by the uterine veins, curves over the ureter about 2 cm from the cervix and reaches the
uterus at the level of the isthmus. There it divides into a de­scending cervical branch and an ascending branch. The latter branch ascends tortuously along the side of the uterus and anastomoses with the ovarian artery via the tubal branch. The best sites for recording Doppler signals are the main trunk of the uterine artery and the origin of the ascending branch. Both vessels can be clearly identified in those areas and can be scanned at an optimum beam–vessel angle.
Advantages of transvaginal scanning. According to our studies, the transvaginal approach has several major advantages over transabdominal scanning, especially in early pregnancy ex­aminations
5
:

Normal Development of Uterine Artery Doppler Spectra

Accurate overall assessment of uterine perfusion
Greater pulsatility of blood flow, allowing better recognition of impedance criteria in the Doppler scan
Smaller range of error owing to a more favorable beam–ves­sel angle
Normal Development of Uterine Artery Doppler Spectra
The Doppler spectra of the uterine arteries display characteris­tic changes from early pregnancy until the conclusion of tro­phoblastic invasion in midpregnancy (Fig. 14.
Doppler spectra in early pregnancy. At the start of pregnancy, the Doppler spectra of the uterine arteries do not differ from those recorded in the periovulatory period. Highly variable patterns can occur. The spectra typically have a sharp systolic upstroke and downstroke with a sharp, narrow systolic peak and a low maximum frequency shift. A variable notch may ap­pear in the systolic downstroke. The diastolic phase of the car­diac cycle consistently shows a very low frequency shift whose
1).
pattern changes more characteristically with advancing gesta­tion than the systolic peak. During the first trimester the sharp systolic downslope typically ends in an early diastolic notch,
which may convert to reverse flow during the initial weeks.
The postsystolic notch is followed by a diastolic peak that shows the highest velocities in the diastolic part of the cardiac cycle during the first trimester. The end-diastolic frequency shift is low in the first trimester, and absent or reverse flow is seen in rare cases. These normal features during early preg­nancy are useful for the visual interpretation of Doppler
waveforms in cases where abnormalities develop later in the pregnancy.
Changes after the first trimester. The characteristic changes past the first trimester are a continued increase in the systolic maxima with broadening of the systolic peak and an increas­ingly high diastolic frequency shift, with disappearance of the early diastolicnotch. The increase in flow velocities is relatively
greater at end diastole than in systole. The angle between the systolic downstroke and the maximum diastolic frequencies becomes greater, and there is an overall flattening of the spec­tral waveform. Generally this development is completed in the 20th week of gestation or by the 24th week at the latest.
Obstetric Ultrasound
Fig. 14.1 Comparison of uterine Doppler spectra recorded during
the first half of pregnancy.The maximum frequency shift in each spec­trum can be read on the adjacent scale. Arrows = systolic notch;
N = early diastolic notch.
Normal Values in Early Pregnancy
Progression of values from weeks 4 to 24. In a prospective
longitudinal study, the progression of normal values for Dopp­ler ultrasound parameters was documented from the 4th to 24th weeks of menstrual age. Of 257 pregnancies examined, 79 met the criteria for inclusion in the study (confirmed dates at examination, no significant uterine anomalies, uncomplicated singleton pregnancy, term delivery of a healthy eutrophic in­fant) based on a retrospective postpartum review. A maximum of 117 individual examinations of the uterine vessels could be evaluated. In addition to the standard indices, the early dias­tolic notch frequency and maximum diastolic frequency were also determined. The latter quantities were used to calculate an index, the notch/peak (N/P) ratio, which characterizes the presence or absence of an early diastolic notch in the spectral
waveform. The data from both uterine arteries were used in calculating all the indices. The following instruments were available for the study: Combison 320–5 combined with the D
300 Doppler unit (Kretztechnik, 5 MHz vaginal probe) and the 128 XP/10 color Doppler unit (Acuson Corp., 5 MHz vaginal probe). SAS software from the Department of Medical Informa­tion and Biometry of Aachen Medical College was used for statistical analysis. The progressions of normal values for the S/D ratio, resistance index (RI), pulsatility index (PI), and N/P ratio are summarized in Table 14.
1.
125
Screen for Preeclampsia and Uteroplacental Insufficiency
Table 14.1 Normal values of uterine artery Doppler indices from the 4th to 24th weeks menstrual age
Weeks n Mean SD P5 P10 P50 P90 P95
S/D ratio (n = 100)
4– 6 14 12.18 8.14 4.87 6.44 10.26 15.45 38.50
7– 9 13 9.54 3.68 4.92 5.53 7.92 13.90 16.77 10–12 8 5.97 4.62 2.86 2.86 4.04 16.75 16.75 13–15 16 3.89 1.59 2.15 2.50 3.47 7.08 7.20 16–18 24 *2.87 1.32 1.97 2.06 2.43 3.70 6.14 19–21 13 2.38 0.37 1.79 1.82 2.37 2.80 2.83 22–24 12 2.14 0.21 1.64 1.99 2.12 2.39 2.45
RI (n = 104)
4– 6 15 0.89 0.04 0.79 0.84 0.89 0.95 1.00
7– 9 13 *0.87 0.04 0.79 0.80 0.86 0.93 0.93 10–12 8 0.76 0.09 0.65 0.65 0.74 0.93 0.93 13–15 16 0.69 0.07 0.56 0.59 0.70 0.81 0.81 16–18 26 *0.61 0.08 0.49 0.51 0.60 0.72 0.75 19–21 14 0.56 0.06 0.44 0.45 0.56 0.63 0.64 22–24 12 0.52 0.05 0.39 0.49 0.53 0.57 0.58
14
PI (n = 102)
4– 6 15 3.32 0.78 1.85 2.36 3.39 4.37 4.80
7– 9 13 2.85 1.07 0.87 1.94 2.53 4.52 4.76 10–12 8 2.12 0.92 1.17 1.17 1.93 3.93 3.93 13–15 16 1.86 0.50 0.85 1.02 2.04 2.29 2.59 16–18 25 *1.25 0.61 0.73 0.79 1.09 1.94 2.93 19–21 13 1.06 0.24 0.66 0.77 1.02 1.44 1.52 22–24 12 0.87 0.23 0.52 0.72 0.82 0.99 1.49
N/P-Ratio (n = 99)
4– 6 15 0.595 0.18 0.10 0.44 0.67 0.74 0.80
7– 9 13 0.628 0.17 0.30 0.41 0.67 0.80 0.85 10–12 8 0.871 0.08 0.71 0.71 0.89 0.99 0.99 13–15 14 0.924 0.10 0.76 0.78 0.94 1.07 1.07 16–18 26 1.03 0.15 0.69 0.86 1.06 1.18 1.22 19–21 12 1.05 0.08 0.91 0.96 1.05 1.15 1.16 22–24 11 1.07 0.07 0.95 0.98 1.11 1.14 1.15
* Significant difference relative to previous value

Early Doppler Examination of Uteroplacental Blood Flow in Abnormal Pregnancy

126
Patients
Inclusion and exclusion criteria. This series consists of 25 preg-
nancies that were examined by transvaginal Doppler sonography before the 25th week of gestation and had an abnormal course or outcome. Inclusion criteria were confirmed dates at the time of the examination, a singleton pregnancy, the development of PIH (dias-
tolic blood pressure ⬎90 mmHg in multiple readings) with or
without proteinuria (300 mg/day), perinatal asphyxia based on
histologically confirmed placental insufficiency, and the delivery of
a growth-retarded infant (10th weight percentile after Ho­henauer). Pregnancies with premature delivery, fetal and/or chro­mosome anomalies, and early pregnancy loss 16 weeks were ex­cluded from the study.
Analysis. The methodology and statistical tools were the same as described above. Statistical significance measured by the 10th and 90th quantiles was determined with the independent t-test with a significance level of
values were of limited validity because of the high prevalence in the selected at-risk population.
α = 0.05. The positive and negative predictive
Early Doppler Examination of Uteroplacental Blood Flow in Abnormal Pregnancy
Results
Maternal parameters such as age and number of pregnancies and deliveries did not differ from those in the normal group. Significant differences were seen mainly in the length of pregnancy (x =31.8
weeks, SD = 8.0 weeks), birthweight (x = 2009 g, SD = 1285 g), and
in the one- and five-minute Apgar scores.
Doppler parameters. None of the Doppler parameters showed sig­nificant dif ferences from a normal pregnancy during the first
trimester. Table 14.2 shows the data on specificity, sensitivity, and
predictive values from weeks 13–15 to weeks 22–24.It is not until
week 16, and thus after the end of the first trimester, that individual
values for the S/D ratio, RI, and PI exceeded the 90th quantile or in­dividual values for the N/P ratio fell below the 10th quantile for a normal pregnancy.
PI. With advancing gestation, the Doppler findings increasingly re-
flected the delayed maturation of uterine perfusion. The PI pro-
vided the best discrimination: 4 of 9 cases in weeks 16–18, 5 of 7 cases in weeks 19–21, and all 8 cases in weeks 22–24 were above
the 90th percentile. Starting in week 19, the PI showed a sensitivity of 87% and a specificity of 92%. The results for the S/D ratio and RI
were slightly lower.
N/P ratio. The N/P ratio, which expresses whether an early diastolic notch is present, had a mean value ⬎1 starting in weeks 16–18 of uncomplicated pregnancies. This parameter also showed increas­ing sensitivity after 16 weeks. Reaching 83 % by week 19 (n = 15), the sensitivity of the N/P ratio was slightly lower than that of the stan­dard Doppler indices.
Discussion
Opening of the spiral arteries. The visible waveform changes in
the uterine vessels, like the progression of the calculated in­dices, reflect the morphological processes in the terminal
vascular bed that are causing progressive dilatation of the spi­ral arteries. The variability of the frequency spectra seen during the initial weeks may be attributable to differences in en­dovascular trophoblastic invasion and to individual factors such as hormone levels and vascular calibers show that it is not possible to distinguish between normal and delayed or impaired perfusion during the first trimester. The significant difference from weeks 13–15 to weeks 16–18 indi­cates that a disproportionately large decrease in vascular re­sistance occurs at the start of the second trimester. This may reflect increasing uterine perfusion after the spiral arteries have opened toward the intervillous space
Secondary trophoblastic invasion. Secondary trophoblastic in-
vasion is crucial for the development of uteroplacental blood flow. The characteristic Doppler changes that occur during this period are a rise in maximum flow velocities throughout the cardiac cycle with a relative predominance in diastole and a flattening or disappearance of the early diastolic notch (in
weeks 16–18 on average). A key observation is that there was no case in which uterine blood flowdeveloped normally at first and then became abnormal secondarily. At the same time, it
was common to find a late onset of normal blood flow with dis­appearance of the early diastolic notch by the 24th week of ges-
7
.
6
. Our results
Table 14.2 Accuracy of uterine artery Doppler examination from the 13th to 24th weeks of menstrual age in predicting the development of pregnancy-induced hypertension or uteroplacental insufficiency
Weeks n Sensi-
tivity (%)
S/D ratio
13–15 2 0 93 0 88 16–18 8 37.5 92 60 92 19–21 6 67 92 80 86 22–24 7 100 92 87.5 100 19 13 85 92 85 92
RI
13–15 2 50 93 50 93 16–18 8 25 92 50 79 19–21 6 33 92 33 67 22–24 7 100 92 87 100 19 13 69 92 82 85
PI
13–15 2 0 94 0 88 16–18 9 44.5 92 67 83 19–21 7 71.5 93 83 87 22–24 8 100 92 89 100 19 15 87 92 87 92
N/P ratio
13–15 2 50 93 50 93 16–18 9 44.5 92 67 83 19–21 7 57 92 80 78 22–24 8 87.5 91 87.5 91 19 15 83 91 84 85
tation. Aristidou et al.
1
Speci-
ficity
(%)
Positive predictive
value (%)
Negative predictive value (%)
attribute this to a delayed but otherwise normal process of trophoblastic invasion and placental matu­ration.
Correlation of Doppler findings with pregnancy disorders. The study results indicate that Doppler sonography is a proven method for the early detection of decreased uterine perfusion.
The results also show that pregnancies that are at risk for developing a hypertensive disorder and/or uteroplacental in­sufficiency can be predicted with increasing confidence in early pregnancy and that a definite correlation exists with the development of uterine perfusion during the period of second­ary trophoblastic invasion. The results of Steel et al.
11
in partic­ular indicate that the sensitivity of early Doppler ultrasound screening correlates with the severity of the developing preg­nancy disorder.
An abnormal uterine artery Doppler finding may also re­flect the presence of chromosomal and/or fetal anomalies, however (reference 1 and authors’ studies). Kuhlmann et al. claim that the cause is placental undervascularization result­ing from arrested or delayed angiopoiesis.
Obstetric Ultrasound
8
127
Screen for Preeclampsia and Uteroplacental Insufficiency
How to proceed when decreased uterine perfusion is found.
The diagnosis of decreased uterine perfusion warrants further testing and also a therapeutic response. When anomalies have been excluded, treatment may consist of a recommendation for rest, early hemodilution, or aspirin therapy. There are still no definitive data on the most effective treatment options.
We recommend that the following steps be taken when decreased uterine perfusion is diagnosed in the 19th or 20th week of gestation:
Exclude a chromosomal and/or fetal anomaly.
Recommend physical rest.
Treatment with aspirin, hemodilution, or NO donors may be
tried in controlled studies.
Reexamine the patient at 24 weeks. If uterine perfusion is still decreased, continue treatment with close-interval preg­nancy surveillance.

Summary

Characteristic changes in the Doppler sonogram. Doppler
sonography of the uterine vessels is proving to be a suitable
14
method for assessing the development of the terminal uterine vascular branches to a low-impedance system and for in­directly following the progression of morphological changes, especially in the spiral arteries. The characteristic changes in the Doppler sonogram consist of a relativelygreater increase in frequency shifts during the diastolic phase of the cardiac cycle compared with systole. This causes a decrease in Doppler in­dices until the middle of the pregnancy and a disappearance of the early diastolic notch (on average, during postmenstrual weeks 16–18).
Given the high variability of Doppler waveforms during the first trimester, it is not possible to discriminate between nor­mal and abnormal perfusion until the start of the second trimester.
Diagnostic accuracy. The diagnostic accuracy of Doppler sono­graphy increases with advancing gestation and is maximal be­tween weeks 19 and 24. At this time a definite correlation ex­ists between an abnormal Doppler sonogram and the sub­sequent development of preeclampsia and/or uteroplacental insufficiency.
The diagnostic value of early Doppler scanning of the uterine arteries is that pregnancy complications can be de­tected at an early stage and therapeutic measures can be insti­tuted to prolong the pregnancy. The ultimate goal is to reduce the high morbidity and mortality of very early prematurity. Ef­fective treatment options still need to be developed and eval­uated, however.
Screening. It remains unclear whether Doppler sonography should be used as a routine screening test. It seems prudent to include examination of the uterine vessels in routine screening at 19–22 weeks, even in patients who have no obvious risk fac­tors.
The early diagnosis of pronounced uteroplacental insuffi­ciency brings us closer to the goal of reducing the high morbid­ity and mortality of early prematurity by prolonging the preg­nancy. Effective treatment options still need to be developed and evaluated.
References
1 Aristidou A, van den Hof MC, Campbell S, Nicolaides K: Uterine artery
Doppler in the investigation of pregnancies with raised maternal serum alphafetoprotein. Brit. J. Obstet. Gynaecol. 97 (1990) 431
2 Bieniarz J, Yoshida T, Romero-Salinas G, Curuchet E, Caldeyro-Barcia R,
Crottogini JJ: Aortacaval compression by the uterus in late human pregnancy.IV. Circulatory homeostatis by preferential perfusion of the placenta. Amer. J. Obstet. Gynecol. 103 (1969) 19
3 Brosens I, Robertson VB, Dixon HG: The physiological response of the
vessels of the placental bed to normal pregnancy. J. Pathol. Bacterial 93 (1967) 569
4 De Ziegler D, Bessis R, Frydman R: Vascular resistance of uterine arter-
ies: physiological effects of estradiol and progesterone. Fertil. Steril. 55 (1991) 775
5 Funk A, Jörn H, Fendel H: Abdominale versus transvaginale Doppler-
Sonographie der uterinen Gefäße. Ultrasch. Klin. Prax. 7 (1992) 264
6 Goswamy RK, Steptoe PC: Doppler ultrasound studies of the uterine
arteries in spontaneous ovarian cycles. Hum. Reprod. 3 (1988) 721
7 Hustin J, Schaaps J-P: Echocardiographic and anatomic studies of the
maternotrophoblastic border during the first trimester of pregnancy.
Amer. J. Obstet. Gynecol. 157 (1987) 162
8 Kuhlmann RS, Werner AL, Abramowicz J, Warsoff SL, Arrington J, Levy
DL: Placental histology in fetuses between 18 and 23 weeks› gestation with abnormal karyotyp. Amer. J. Obstet. Gynecol. 163 (1990) 1264
9 Perrot-Applanat M, Groyer-Picart MT, Garcia E, Lorenzo F, Milgram E:
Immunocytochemical demonstration of estrogen and progesterone receptors in muscel cells of uterine arteries in rabbits and humans. En­docrinology 123 (1988) 1511
10 Rudolph AM, Heyman MA: Circulatory changes during growth in fetal
lamb. Circ. Res. 26 (1970) 289
11 Steel SA, Pearce JM, Mc Parland J, Chamberlain GVP: Early doppler ul-
trasound screening in prediction of hypertensive disorders of preg­nancy. The Lancet 335 (1990) 1548
12 Weiner Z, Thaler I, Levron J, Lewit N, Itskovity-Eldor J: Assessment of
ovarian and uterine blood flow by transvaginal color Doppler in ovar­ian-stimulated women correlation with the number of follicles and steroid hormone levels. Fertil. Steril. 59 (1993) 743
128
Normal Fetomaternal Doppler Indices in the Second and
15
Third Trimesters of Pregnancy
A. K. Ertan, H. J. Hendrik, I. Tossounidis, and W. Schmidt

Establishing Normal Curves

The goal of defining normal values for fetomaternal perfusion is to be able to discriminate between normal and abnormal pregnancies on the basis of Doppler ultrasound findings. This requires the establishment of reference values and normal
values for physiological conditions of flow
“Ideal” course of pregnancy. Not infrequently, normal values are based on data from pregnancies that must meet a set of normal criteria and thus represent more of an “ideal” case. Be­cause of this selection effect, the defined cutoff limits may be too narrow for at best they describe the variability of “ideal
values” rather than the original biological scatter
Dependence on gestational age. Perfusion changes have been described with advancing gestation due to maturation of the trophoblastic tissue, and these changes must be considered in the interpretation of reference curves. It is best, therefore, to use gestational-age-based charts to express the normal values for particular indices. Measurements should commence at a stage of the pregnancy when the results of the measurements can still influence obstetric management. The current consen-
8
.
27
.
sus is that this is the mid-second trimester of pregnancy, when fetal viability is reached. There are also cases in which the analysis of maternal arterial waveforms can be rewarding in earlier weeks of pregnancy
Cross-sectional studies. In a cross-sectional study design, the measurements should be spaced as evenly as possible over the study period, obtaining an adequate number of measurements for the various weeks of pregnancy, such as more than 15 per
13
week pregnancy as this might narrow the tolerance ranges by reduc­ing the variability relative to the natural biological scatter
more favorable prognosis for pregnancies that are at risk by their history and/or findings but exhibit normal blood flow patterns. This also requires the analysis of populations with ab­normal pregnancies signed to show the distribution of normal values for the Dopp­ler indices that are most commonly used to characterize feto­maternal blood flow.
. It is best to avoid multiple measurements in any one
The goal of establishing normal reference curves is to offer a
16
.
20
. The curves presented below are de-
9
.
Obstetric Ultrasound

Methodology

Defining the Normal Population
Our normal population consisted of patients whose dates had been confirmed by an ultrasound examination before the 20th
week of pregnancy. We excluded cases that had a primary ce­sarean section for placental insufficiency and cases with an ab­normal fetal heart rate (FHR) trace or impending intrauterine asphyxia. The birthweights in the normal population were be­tween the 10th and 90th percentiles for gestational age as de­fined as Roemer et al.
were 7 or higher, and the umbilical artery pH was 7.20 or higher. We also excluded multiple pregnancies and cases with fetal anomalies.
Plotting Quantile Curves
Indices. The qualitative analysis of recorded Doppler wave-
forms has proved to be a more useful clinical tool than the more complex calculation of volume flow. This is reasonable
18
. The 5- and 10-minute Apgar scores
when we consider that a quantitative analysis requires the measurement of small vascular cross sections, and this adds a potential source of error.
Numerous indices have been devised for the qualitative analysis of Doppler waveforms (review in reference 8). The fol­lowing are the most commonly used (Fig.15.
The S/D ratio of Stuart (1980)
The resistance index (RI) of Pourcelot (1974)
The pulsatility index (PI) of Gosling and King (1977)
The following quantities are used in analyzing the Doppler
sonogram and calculating the indices:
S = maximum peak systolic frequency
D = maximum end-diastolic frequency
Tav = temporal average of maximum frequency
D = instantaneous spatial average frequency
E = temporal average of spatial average frequencies
22
1):
17
11
129
Normal Fetomaternal Doppler Indices in the Second and Third Trimesters of Pregnancy
In some ultrasound systems, the temporal average of the maxi-
kHz
S/D ratio =
Resistance Iindex(RI): S–D
Tav
S
D
Time
S
Pulsatility index (PI): S–D
Tav
S D
Fig. 15.1 Parameters used for qualitative waveform analysis.
S = maximum systolic frequency, D = maximum end-diastolic frequency, Tav = temporal average of maximum frequency.
The indices are calculated from the maximum systolic (S) and end-diastolic (D) frequency shifts and, in the case of the PI, from the maximum frequency shift averaged over the entire cardiac cycle (Tav) using these formulas (Fig. 15.
S/D ratio=
15
RI =
S
D
S–D
1):
S
S–D
PI =
Tav
mum frequencies (E) is used in calculating the PI. This results in correspondingly higher values.
In the studies published to date, no definite advantage has been found for any single parameter dices express a ratio, they are largely independent of the in­sonation angle. The S/D ratio is very easy to determine, and the RI is easy to interpret: values close to 0 signify a very low flow resistance, while a value of 1 indicates cessation of flow. The PI, however, is the only index that can provide differentiated in­formation on an absence of end-diastolic flow, because the average maximum frequency shift contains information on the cardiac cycle as a whole, while the S/D ratio tends towardinfin­ity and the RI equals 1 in cases with absent end-diastolic flow.
Quantiles. Our calculation of normal values was based on 602 pulsed Doppler flow measurements in 370 patients who met the normal population criteria defined above. An average of
1.62 measurements were acquired per patient. Quan tiles were determined as a function of gestational age, since the Doppler values did not show a normal distribution. The study period was divided into intervals of two consecutive gestational weeks each, and the 5th, 10th, 50th, 90th, and 95th quantiles were calculated and plotted graphically for each interval. The curves were smoothed by cubic regression. In the first example given below, both the smoothed and original curves are shown. Since the smoothing did not significantly alter the curve shape, only the smoothed curves are presented in the figures below. Th e 5th, 10th, 50th, 90th, and 95th quantiles are shown for each of the measured indices.
6, 8, 9–11
. Because all the in-

Results

Figures 15.2–15.14 show the reference curves obtained for the S/D ratio, PI, and RI of the umbilical artery, fetal aorta, middle
6
5
4
Umbilical artery
S/D
3
2
1
0
26
28 30 34
32 36 38 40 42
Weeks of gestation
p95 p90 p50 p10 p5
cerebral artery, and uterine artery. Figure 15. erence curves for the cerebroplacental ratio.
6
5
4
Umbilical artery
S/D
3
2
1
0
28 30 34
26
32 36 38 40 42
Weeks of gestation
15 shows the ref-
p95 p90 p50 p10 p5
130
Fig. 15.2 Reference curves for the S/D ratio of the umbilical artery, based on 600 measurements in normal pregnancies and grouped by
even gestational weeks.
Fig. 15.3 Reference curves for the S/D ratio of the umbilical artery, based on 600 measurements in normal pregnancies and grouped by even gestational weeks. The curves were smoothed by cubic regres­sion.
Results
1.0
0.8
0.6
Umbilical artery
RI
0.4
0.2
0
28 30 34
26
32 36 38 40 42
Weeks of gestation
p95 p90 p50 p10 p5
Fig. 15.4 Reference curves for the RI of the umbilical artery, based on 600 measurements in normal pregnancies and grouped by even gestational weeks. The curves were smoothed by cubic regression.
12
10
Fetal aorta
8
6
S/D
4
2
p95 p90 p50 p10 p5
1.8
1.6
1.2
Umbilical artery
PI
0.8
0.4
0
26
28 30 34
32 36 38 40 42
Weeks of gestation
p95 p90 p50 p10 p5
Fig. 15.5 Reference curves for the PI of the umbilical artery, based on 510 measurements in normal pregnancies and grouped by even gestational weeks. The curves were smoothed by cubic regression.
1.0
0.8
Fetal aorta
0.6
RI
0.4
0.2
p95 p90 p50 p10 p5
Obstetric Ultrasound
0
28 30 34
26
32 36 38 40 42
Weeks of gestation
Fig. 15.6 Reference curves for the S/D ratio of the fetal aorta, smoothed by cubic regression.
3.0
2.5
Fetal aorta
2.0
PI
1.5
1.0
0.5
0
28 30 34
26
32 36 38 40 42
Weeks of gestation
p95 p90 p50 p10 p5
0
28 30 34
26
32 36 38 40 42
Weeks of gestation
Fig. 15.7 Reference curves for the RI of the fetal aorta, smoothedby cubic regression.
14
12
10
8
S/D
6
Middle cerebral artery
4
2
0
28 30 34
26
32 36 38 40 42
Weeks of gestation
p95 p90 p50 p10 p5
Fig. 15.8 Reference curves for the PI of the fetal aorta, smoothed by cubic regression.
Fig. 15.9 Reference curves for the S/D ratio of the middle cerebral artery, smoothed by cubic regression.
131