Umbilical Doppler Velocimetry: Normative Data and Diagnostic Efficacy

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The umbilical artery was the first fetal vessel to be evaluated by Doppler velocimetry and has since become the most widely investigated component of the fetal circulation. The attention paid to this vessel may be explained partly by its ready accessibility to Dop- pler interrogation, even without guidance by duplex imaging, and because it is a vital component of the fetal circulation, acting as the lifeline between the fetus and the placenta. Numerous studies have reported the methodology of Doppler interrogation of the umbilical artery and have elucidated the factors that modulate the umbilical arterial Doppler indices under normal conditions. This chapter describes the procedure of Doppler sonography of the umbilical circulation and reviews the normative data on the umbilical arterial Doppler indices.

Doppler Interrogation of the Umbilical Artery

Doppler interrogation of the umbilical arterial circulation is a relatively simple procedure that does not re- quire a large block of time. Consistent with the general approach for conducting fetal surveillance tests, the mother should be counseled regarding the reason for the test, the nature of the information generated by the device, its reliability and safety, and other relevant issues. Similar to the practice for fetal heart rate monitoring, the mother lies in a semirecumbent position with a slight lateral tilt, which minimizes the risk of de- veloping supine hypotension syndrome due to caval compression. The examination should be conducted only during fetal apnea and in the absence of fetal hic- cup or excessive movement. Umbilical arterial circulation is amenable to interrogation by either a continuous-wave Doppler device or a pulsed-wave Doppler duplex system. The procedure of Doppler insonation var- ies with the choice of Doppler mode.

Continuous-Wave Doppler Interrogation

Continuous-wave Doppler interrogation of the umbilical artery is one of the simplest procedures available for fetal surveillance. However, it is now seldom used

in clinical practice. The procedure is conducted using a freestanding Doppler instrument with an integrated fast Fourier transform-based spectrum analyzer. The transducer is usually a pencil-shaped probe with an operating frequency of 2±4 MHz. The transducer is placed on the mother's abdomen overlying the fetus with an acoustic coupling jelly intervening between the transducer face and the maternal abdominal skin.

The method is similar to that used for listening to fetal heart tones with the simpler Doppler devices. The transducer is systematically manipulated to obtain the characteristic Doppler frequency shift waveforms from the umbilical artery, which is seen on the device display. The process of identification is facilitated by listening to the typical audible sound of the Doppler shift. The process of Doppler pattern recognition is relatively simple, can be readily mastered, and is not prone to significant subjective variations. Complete Doppler interrogation of the cord can be ensured by obtaining the umbilical venous Doppler signals simul- taneously with the arterial signals (Fig. 10.1).

Umbilical Doppler Velocimetry:

Normative Data and Diagnostic Efficacy

Dev Maulik

Fig. 10.1. Continuous-wave Doppler interrogation of umbilical vessels. Doppler frequency shift recordings above the baseline are derived from the umbilical arteries, and those below the baseline are from the umbilical vein

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Pulsed-Wave Doppler Interrogation

Pulsed Doppler sonography has become the most fre- quently used mode for umbilical arterial interrogation.

With a pulsed-wave duplex Doppler system, an obstetric scan is initially performed, and loops of the umbilical cord are identified. Unlike the continuous-wave mode, pulsed-wave Doppler insonation permits selec- tion of the location in the cord for interrogation. As discussed below, the site of interrogation in the cord affects the configuration of the Doppler waveform.

Usually a free-floating portion of the cord is insonated.

The cursor line representing the beam path is aligned to intersect the selected portion of the cord, and the Doppler sample volume is placed in that location.

The Doppler mode is then activated, and the umbilical arterial Doppler waveforms are obtained (Fig. 10.2).

Doppler Display and Archiving

The Doppler waveforms are exhibited on the video monitor of the continuous-wave or the duplex device.

Being generated in real time, the waveforms are scrolled from right to left on the screen. The screen is frozen when appropriate signals are displayed, and the desired measurements are performed on these waveforms. Usually, three to five waveforms are measured, and the individual results are averaged and shown on the screen. The display along with the results can be printed, and the print, can be archived. The display and results may also be saved on a video tape recorder when a duplex system is used and on an audio tape recorder when continuous-wave insonation is used.

Descriptor Indices

of the Umbilical Arterial Doppler Waveform

The Doppler frequency shift information from the umbilical artery is predominantly utilized to assess downstream impedance in the fetoplacental vascular bed. As discussed in Chap. 4, it is accomplished by calculating indices that analyze the pulsatility of the waveform in an angle-independent manner. Of the numerous indices described in the literature, the systolic/diastolic (S/D) ratio, resistance index (RI), and pulsatility index (PI) are most commonly used in clinical practice. The relative merits of the commonly used indices are discussed in Chap. 4.

The comparative diagnostic efficacy of the above Doppler indices and the diastolic/average (D/A) ratio for predicting adverse perinatal outcome was investigated by Maulik and associates [1] in a prospective blinded study in a high-risk pregnancy population. A continuous-wave Doppler device with a 4-MHz transducer was used. The analytic technique consisted of the receiver operating characteristic (ROC) method, which evaluates a test's ability to discriminate the dis- eased from the nondiseased population. The ROC curves showed that the RI had the best discriminatory ability when compared with other Doppler indices, and the PI fared the worst (Fig. 10.3). The area under the ROC curve of these indices showed that these differences were statistically significant (Ta- ble 10.1). Despite its limitations, the S/D ratio remains the most widely used Doppler index for evalu- ating the fetal circulation, especially for umbilical ar-

Fig. 10.2. Pulsed Doppler interrogation of umbilical arteries. Left: Two-dimensional sonogram depicting the flow mapping of the umbilical vessels and placement of the Doppler sample volume at the umbilical arterial location.

Right: Umbilical arterial Dop- pler waveforms

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terial hemodynamics. Such usage is attributable mostly to widespread knowledge of the S/D ratio within the obstetric community and to the apparent simplicity of the index. In practice, the choice of an index may not significantly affect the clinical efficacy of an umbilical arterial Doppler investigation.

Reproducibility of Umbilical Arterial Doppler Indices

A critical factor to the utility of a test is its precision, which is defined as the degree to which a measured variable is reproducible. The reproducibility of a Dop- pler index is determined by all factors that contribute to the variance of that index (see Chap. 4). The variance is affected by hemodynamic and nonhemodynamic factors [2]. The hemodynamic factors may be physiologic, such as gestational age-dependent changes and those associated with fetal breathing, or pathologic, such as maternal preeclampsia or fetal growth restric- tion. The nonhemodynamic factors constitute the error component, which includes intra- and interobserver variations. Although the latter factors are important when considering the precision of the technique, hemodynamic variations are the principal determinations of the variance of the umbilical Doppler indices [2].

Maulik and colleagues [2] prospectively investigated the reproducibility of the umbilical arterial Doppler indices (S/D ratio, RI, PI, D/A) in terms of the proportion of variance attributable to intra- and interobserver errors. A continuous-wave Doppler instrument with a 4-MHz transducer was used. The analytic method in- volved determination of the intraclass correlation using analysis of variance. For the various indices, the proportion of total variance attributable to intra- and interobserver errors varied between 4% and 8%

and 9.8% and 14.3%, respectively. These results are comparable to those of other investigators [3±7] and are summarized in Table 10.2. As is evident, umbilical Fig. 10.3. Receiver operating characteristics curve of umbil-

ical arterial Doppler indices. RI resistance index; S/D systolic/diastolic ratio; D/A diastolic/average ratio; PI pulsatile index. Data points are measured values of indices. (Reprinted from [1] with permission)

Table 10.1. Receiver operating characteristic curve areas of Doppler indices (modified from Maulik et al. [1])

Indices AreaÔSE Significance (p) of the difference in the ROC areas vs S/D vs D/A vs PI RI 0.921Ô0.021 <0.05 < 0.05 <0.001 S/D 0.905Ô0.019 >0.05 <0.001

D/A 0.887Ô0.029 <0.006

PI 0.803Ô0.023

SE, standard error; ROC, receiver operating characteristic;

RI, resistance index; S/D, systolic/diastolic ratio; D/A, diastolic/average ratio; PI, pulsatility index.

Table 10.2. Reproducibility of the umbilical arterial Doppler indices

Study Doppler index Interobserver Intraobserver

Reliability Variation (%) Reliability Variation (%)

Schulman et al. [3] S/D 6

Nienhuis et al. [4] PI 0.74 0.62

Maulik et al. [2] RI 0.89 11 0.95 5

S/D 0.91 10 0.96 4

PI 0.86 14 0.92 8

Gudmundsson et al. [5] PI 8

Davies et al. [6] RI 7

PI 12

S/D 11, 15

Scherjon et al. [7] PI 0.39 0.91

S/D, systolic/diastolic ratio; PI, pulsatility index; RI, resistance index.

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arterial Doppler indices demonstrate satisfactory precision for clinical applications.

Continuous-Wave Versus Pulsed-Wave Doppler Indices

Although one may not expect any discrepancy between the Doppler indices obtained by continuous- wave or pulsed-wave Doppler interrogation, in practice there are enough differences between these tech- niques to warrant an objective inquiry into the issue.

Brar and associates [8] compared the S/D ratios obtained by continuous-wave and pulsed-wave Doppler ultrasonography from the umbilical artery in high- risk pregnancies during the third trimester and found no significant difference in the mean S/D ratios obtained by either method for the entire population (continuous-wave S/D 2.81Ô1.79, pulsed-wave S/D 2.71Ô1.83; r=0.98), the normal group (continuous- wave S/D 1.96Ô0.41, pulsed-wave S/D 1.95Ô0.40, r=0.91), or the abnormal group (continuous-wave S/D 6.23Ô1.58, pulsed-wave S/D 6.35Ô1.52, r=0.94).

Mehalek and coinvestigators [9] also observed no significant differences (p>0.05) between the continuous- wave and pulsed-wave Doppler devices when measuring the peak S/D ratios in the umbilical arteries. The S/D ratios of the umbilical artery measured by each device showed a strong correlation, whether measured by one observer (r=0.93) or two observers (r=0.89). Most other investigations corroborated this finding [5, 10].

In contrast to the above investigators, van Vugt and coinvestigators [11] found that the AB ratio (same as the S/D ratio), RI and PI were slightly higher for the continuous-wave Doppler system compared to the pulsed-wave Doppler system, but not significantly (p=0.18, p=0.21, and p=0.44, respectively).

The authors speculated that the difference in the sig- nal-to-noise ratio (S/N ratio) between the pulsed- wave and continuous-wave Doppler systems was the reason for the discrepancy. Jorn and associates [12]

also observed differences between duplex pulsed Dop- pler and nonduplex continuous-wave and pulsed-wave Doppler systems in terms of their clinical efficacy.

The sensitivity was higher with the simple nonduplex Doppler technique (74.3% versus 52.9%), whereas the specificity was higher with the duplex Doppler technique (77.9% versus 52.6%). The authors thought that this finding was attributable to the inability to local- ize the vessel precisely using the simpler stand-alone Doppler devices. Gaziano and colleagues [13] reported the use of a threshold value of 4.5 for the umbilical arterial S/D ratio derived with pulsed duplex Doppler ultrasonography. This value is considerably higher than the common S/D ratio cutoff value of 3.0 obtained by continuous-wave Doppler insonation.

Despite these differences, most investigators use the same discriminatory threshold values for the Doppler indices irrespective of the type of Doppler instrumentation. Whether it is justifiable remains an open question.

Site of Doppler Interrogation

Introduction of duplex pulsed Doppler ultrasound for interrogation of umbilical arteries allowed determination of the sampling site in the umbilical cord. Utili- zation of this approach led to the realization that the site of Doppler sampling in the umbilical cord may contribute significantly to variations in the Doppler indices. Several studies addressed this issue specifically. Most observed that the location of the Doppler sampling site in the umbilical cord affects the Dop- pler waveform and is reflected in the Doppler indices, which are higher at the fetal abdominal end of the cord than at this placental end [14, 15]. Abramowicz and coinvestigators [15] studied the effect of the examination site in 30 normal pregnancies and noted statistically significant differences (p<0.01±<0.0007) in the umbilical arterial S/D ratio between the two measurement sites. The values (meanÔstandard de- viation) at the placental insertion ranged from 4.2Ô0.4 at 17±20 weeks to 2.1Ô0.5 at 37±40 weeks.

The corresponding values at the fetal abdominal end were 6.1Ô0.8 and 3.3Ô0.5, respectively. In comparison, the continuous-wave Doppler interrogation, which was blind to the site of sampling in the cord, generated values of 4.8Ô1.3 and 2.3Ô0.3, respectively.

Maulik and associates [2] prospectively investigated the components of variance and error contribu- tions of umbilical arterial Doppler indices in a normal pregnant population (308 mothers) with gestational ages ranging from 27 to 40 weeks. In 46 women, duplex pulsed Doppler ultrasound was used to in- terrogate the placental and fetal ends of the cord. The study demonstrated that the site of measurement was a significant source of variance; the PI was affected the most and the D/A ratio the least (Table 10.3). The effect of the measurement site on the umbilical arterial indices was confirmed by Mehalek and colleagues [15] who performed pulsed umbilical arterial Doppler duplex sonography on 58 patients and noted that the Doppler indices were significantly higher at the fetal end of the cord than at the placental end. Because of the dependence of the indices on the size of interrogation, most investigators emphasize the importance of identifying the sampling location in the cord when duplex pulsed Doppler ultrasound is used. Obviously, this point is not an issue with continuous-wave Dop- pler insonation without the imaging guidance.

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The mechanism of this phenomenon was investigated by Vieyres and coinvestigators [16] in a compu- ter model, which showed that placental resistance is the primary factor for the observed differences between the Doppler waveforms from the placental end and from the fetal end of the cord, whereas viscosity and cord length have secondary influences. The phenomenon may be explained more adequately by the concept of impedance and wave reflection (see Chap. 4). The fetoplacental vascular bed is a low-impedance system associated with minimal wave reflection, which explains the presence of continuing forward flow in the umbilical artery during diastole. The closer the measurement site is to the placenta, the less the wave reflection and the greater the end-diastolic flow. Consequently, the Doppler waveform that represents arterial flow velocity demonstrates progressively declining pulsatility and the indices of pulsatility, such as the RI or the S/D ratio.

Not all studies, however, agree with the above findings. Ruissen and associates [17] observed that although the PI values differed among the various lo- cations in the umbilical artery (within the fetal abdomen, 0±5 cm from the origin of the umbilical cord, in the free-floating part, 0±5 cm from its insertion in the placenta) no unequivocal tendency or statistically significant difference in the PI could be demonstrated. The authors concluded that possible variations in the Doppler waveform along the course of the umbilical artery have no clinical relevance in uncomplicated pregnancies.

Short-Term Temporal Variations:

Diurnal Effect

Short-term temporal variations in the umbilical arterial Doppler indices may affect their reproducibility and efficacy and should be taken into account when interpreting changes in the indices. FitzGerald and associates [18] failed to observe any appreciable diurnal changes in the umbilical arterial Doppler wave-

form. This point was further investigated by Hastie and colleagues [19], who recorded umbilical arterial Doppler indices on 3 days in each of 97 women within a 7-day period. No significant day-to-day variations (p>0.05) were noted in the S/D ratio or the PI over the period of study. The degree of variability was greater before 30 weeks' gestation. It appears that after 30 weeks' gestation diurnal variations in the umbilical arterial Doppler indices have a range of daily variability acceptable for clinical or research applications.

Long-Term Temporal Variations:

Gestational Age Effect

As gestation advances, umbilical arterial Doppler waveforms demonstrate a progressive rise in the end- diastolic velocity (Fig. 10.4). This phenomenon was first described by Stuart and associates [20]. The gestational age at which end-diastolic velocity may be first noticed in the umbilical arterial circulation de- pends on the examination technique. It is imperative to ensure that the high-pass filter is either turned off or set at the lowest value irrespective of the sono- graphic approach. In addition, the use of transvaginal Doppler sonography with color flow-assisted pulsed- wave Doppler interrogation significantly improves our ability to identify the end-diastolic velocity during early pregnancy.

Arduini and Rizzo [21] utilized color Doppler- guided transvaginal spectral Doppler sonography and demonstrated that the end-diastolic forward flow may be present in the umbilical artery as early as 10 weeks' gestation. After week 10 the proportion of cases with end-diastolic forward flow progressively increased with the advancing gestation and it was present in almost all cases by about 15 weeks. At this early stage the phenomenon was not noted during every cardiac cycle, although the percentage of cardiac cycles in which end-diastolic velocities were present increased with the progression of pregnancy. In this preliminary experience, the authors found no as- sociation between the PI and the later development of pregnancy complications. Other investigators also noted the presence of end-diastolic velocity in the umbilical artery by 15 weeks [22].

Early investigators, utilizing the transabdominal approach, noted the universal presence of the end- diastolic velocity by about 22 weeks' pregnancy [23].

However, the high-pass filter was set at 200 Hz, which is unacceptably high for this application. Our own experience with transabdominal duplex pulsed-wave Doppler insonation indicates that end-diastolic velocity is detectable at the placental end of the cord in most cases by about 18 weeks' gestation. Thereafter Table 10.3. Location of measurement and reliability of

Doppler indices (modified from Maulik et al. [1] with permission)

Doppler index Reliability

coefficient (%) Error variance (%)

D/A 71 29

S/D 62 38

PI 54 46

RI 68 32

D/A, diastolic/average ratio; S/D, systolic/diastolic ratio; PI, pulsatility index; RI, resistance index.

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the end-diastolic velocity continues to increase throughout the pregnancy, which is expressed by the umbilical arterial Doppler indices (Fig. 10.5). The indices that reflect the Doppler wave pulsatility, such as the RI, S/D ratio, and PI, continue to decrease, whereas the D/A ratio, which is the normalized end- diastolic frequency shift, continues to increase. In a prospective study involving 308 normal pregnant mothers, Maulik and associates [2] quantified the contribution of the duration of pregnancy to the total variance of the umbilical arterial Doppler indices. It was observed that the gestational age was the single major contributor to the total variance of the indices, ranging from 33% for the PI to 46% for the S/D ratio.These trends in the Doppler waveform are consistent with the crucial physiological changes that occur in the fetoplacental circulation characterized by the gestational age-dependent decline in the fetoplacental flow impedance [24]. Anderson and Faber [25] esti- mated that the fetoplacental circulatory resistance in the ovine fetus decreased by 2.8% per day, and during the last third of pregnancy the decrease in resistance was calculated to be tenfold.

The controlling mechanism for this phenomenon remains uncertain. It has been shown in human placental studies that there is continuing expansion of the fetoplacental vascular system throughout the pregnancy [26]. Furthermore, the villous vascular system undergoes a transformation, resulting in the appear- ance of sinusoidal dilation in the terminal villous capillaries as pregnancy approaches term, and more than 50% of the stromal volume may be vascularized.

The progressive decrease in fetoplacental flow impedance is associated with a concomitant decline in the flow wave reflection from the downstream vascular bed, which results in an increase in the end-diastolic velocity. The latter ensures continuing forward flow and perfusion of the fetal placenta during the entire cardiac cycle.

Fetal Heart Rate

Heart rate influences the configuration of the arterial Doppler waveform (see Chap. 4). Thompson and colleagues [27], did not observe any significant effect of fetal heart rate on the umbilical arterial S/D ratio.

The correlation between the fetal cardiac cycle, which is the reciprocal of the heart rate, and the S/D ratio was poor (r=0.1). Other Doppler indices (PI and RI) demonstrated a similar relation with the heart rate.

This finding was contradicted, however, by Mires and associates [28], who specifically investigated the relation between fetal heart rate and the umbilical arterial Doppler indices in 85 normal pregnancies: 25 of Fig. 10.4a±g. Gestational age effect on the umbilical arte-

rial Doppler frequency shift waveforms. Panels are orga- nized from top to the bottom according to the advancing gestation. a Waveforms at 16 weeks. b At 20 weeks. c At 24 weeks. d At 28 weeks. e At 32 weeks. f At 36 weeks.

g At 40 weeks. Note the progressive increase in end- diastolic velocity and the concomitant fall in pulsatility as the gestation advances

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the women were antepartum and 60 were in labor.

Among the antepartum patients, both the S/D ratio and RI had a significant correlation with heart rate (r=±0.49; p<0.02). The intrapartum mothers demonstrated a similar significant negative correlation between the heart rate and the indices (r=±0.65;

p<0.001). A heart rate variation of 117 and 162 bpm resulted in corresponding S/D ratio values of 2.0 and 2.8, respectively. The effect was more pronounced with a wider range of heart rate. For example, when the latter varied between 90 and 175, the S/D ratio changed from 3.4 to 1.7. Thus significant changes in the indices may occur, not because of any changes in the impedance but due to changes in the fetal heart rate, especially when bradycardia is present. Mires et al. concluded that it is important to correct the indices by changing the fetal heart rate.

To address this contradiction, a prospective study was undertaken by Yarlagadda and colleagues [29].

The population consisted of 194 mothers with uncomplicated pregnancies and gestational ages ranging from 27 to 39 weeks. Linear regression of the data grouped in 2-week intervals demonstrated a moderate but statistically significant (p<0.05) correlation between the fetal heart rate and the umbilical Doppler indices. The influence of the heart rate on the indices

was then further analyzed by a multiple regression technique, which demonstrated that 15%±18% of the total variance of the indices was attributable to fetal heart rate effect. Moreover, when the Doppler indices were standardized for a heart rate of 140 bpm and a gestation of 34 weeks, using a multiple regression- based equation the 95% limits of the umbilical artery Doppler indices were reduced by 32%, 34%, 26%, and 32% for D/A, S/D, PI, and RI, respectively. This study corroborated the findings of Mires and coinvestigators [28], that the fetal heart rate significantly influences umbilical arterial Doppler indices.

The mechanism of the heart rate effect on the Doppler indices is discussed in Chap. 4. To recapitu- late briefly, it is well recognized that when the heart rate drops the diastolic phase of the cardiac cycle is prolonged and the end-diastolic frequency shift de- clines. These changes are reflected in the Doppler indices that depict the pulsatility of the Doppler waveform. It has been reconfirmed [30, 31] that the diastolic time is the main component of the changes in the duration of a cardiac cycle (see Chap. 4) and that the effect of the heart rate changes on the Doppler indices is mediated predominantly through the diastolic phase of the cardiac cycle. There is also evi- dence that the fetal heart rate may affect the ability of Fig. 10.5a±d. Changes in the Doppler indices with the

progression of gestation. Changes in S/D, PI, RI, and D/A are depicted in a, b, c, and d, respectively. See legend to Fig. 10.4 for abbreviations. (From [52] with permission)

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the Doppler waveform analysis to reflect completely the changes in the downstream impedance [32].

It remains controversial, however, whether correct- ing the indices for fetal heart rate improves their diagnostic efficacy when the baseline heart rate remains within the normal range. The general consensus is that although the Doppler indices are affected by the fetal heart rate it may not be a significant factor when the rate is within the normal range. For example, Mansouri and colleagues [33] observed in uncomplicated pregnancies that an upper limit of 3.0 for a normal umbilical artery peak S/D ratio was acceptable only if the in- stantaneous fetal heart rate was 130 bpm or higher.

Similarly, Ruhle and coinvestigators [34] found few variations in the umbilical arterial S/D ratio within the normal range of fetal heart rate (120±160 bpm). Most investigators therefore do not recommend correction of the indices for the heart rate.

Breathing

Substantial changes in the intrathoracic pressure and central hemodynamics occur during fetal breathing, leading to dynamic variations in the umbilical arterial Doppler waveform and Doppler indices (Fig. 10.6). The effect of fetal breathing on umbilical arterial indices has been recognized from the early days of Doppler velocimetry and led to the recommendation that the indices should be measured only during fetal apnea [35]. Fetal breathing movement-induced changes in cardiovascu-

lar function were originally reported in the fetal lamb preparation by Dawes and associates [36]. The initia- tion of rapid, irregular respiratory movement in the fetal lambwas often associated with tachycardia and hypertension. Vigorous breathing led to increases in the arterial pressure of as much as 20%. However, transient falls in arterial pressure were also seen coinciding with decreases in the intrathoracic pressure. In addition, there were significant variations in the aortic flow, which declined to 400 ml/min and rose to 900 ml/min from a mean of 650 ml/min.

Chiba and coworkers [37] were the first to report changes in the human fetal venous circulation during fetal breathing movements. Using pulsed-wave Dop- pler ultrasound combined with real-time B-mode imaging, these investigators demonstrated that the umbilical venous blood flow increased with fetal in- spiration (during which the fetal abdominal wall moved inward) and decreased with expiration (during which the wall moved outward). Koppelaar and Wla- dimiroff [38] compared the effect of breathing on the umbilical venous and arterial Doppler waveforms and noted that, in contrast to venous flow velocity, the magnitude of breathing-related modulation of arterial pulsatility was small and independent of breathing amplitude.

In addition to the avoidance of umbilical Doppler interrogation during fetal breathing, there are practi- cal issues to consider. The effect of breathing on the variability of the indices was addressed by Spencer and associates [39], who demonstrated that even dur-

Fig. 10.6. Fetal breathing and umbilical arterial Doppler waveforms. Observe the dynamic variations in the arterial and venous Doppler tracings

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ing the breathing episodes deriving the indices from a minimum of six waveforms ensured coefficients of variation of 10% or less. The issue of the need to use duplex imaging to ensure fetal apnea was addressed by Hoskins and coinvestigators [40], who showed that when stand-alone continuous-wave Doppler units are used to acquire umbilical artery Doppler waveforms during fetal apnea, the presence of apnea can be as- certained using the variability of the arterial and venous trace without using imaging equipment. Our own experience corroborates this finding.

Behavioral States

Behavioral states may be defined as the neurobiologic functional conditions, exemplified by sleep or wake- fulness. These states are characterized by multiple parameters, including open or closed eyes, eye movement, body movement, breathing, and heart rate ac- tivity. Prechtl and Bientema [41] were the first to de- scribe the various behavioral states in neonates. For the human fetus four behavioral states were described by Nijhuis and coworkers [42] based on fetal eye and body movements and the heart rate. Of these states, the quiet sleep state (1F) and the active sleep state (2F) are important considerations for fetal cardiovascular function.

Mulders and associates [35] investigated the effect of fetal behavioral states on 19 normal pregnancies between 37 and 39 weeks' gestation. The fetal heart rate pattern was used to determine states 1F and 2F.

The umbilical arterial PI was noted to be higher during the 1F periods than during 2F. This difference disappeared when the effect of the heart rate was taken into account by normalizing all PI values to the standard heart rate value of 140 bpm. This question was further investigated by van Eyck and coinvestigators [43], who utilized simultaneous measurements of fetal heart rate and eye and body movements. The PI values for states 1F and 2F demonstrated no significant differences and considerable overlaps. This in- sensitivity of the umbilical arterial circulation to behavioral state implies that behavioral states should not be considered when measuring the umbilical arterial Doppler indices.

Blood Viscosity and Doppler Indices

Viscosity is an attribute of a fluid that reflects its in- trinsic resistance to flow. Blood viscosity is a complex phenomenon and is dependent on the plasma and the formed elements. The contribution of viscosity to impedance to flow is defined by Poiseuille's law. With certain pregnancy disorders (e.g., preeclampsia) fetal

blood viscosity has been shown to be increased [44].

The influence of fetal blood viscosity on the umbilical arterial Doppler indices was studied by Giles and Trudinger [45], who observed significantly (p<0.01) higher blood viscosity at high shear in the high-risk group with abnormal Doppler indices. The investigators, regrettably, did not consider the possible effect of gestational age in this analysis. Steel and coinvestigators [46] investigated the contribution of viscosity to the impedance of blood flow in the umbilical artery as determined by the RI for 31 pregnancies complicated by preeclampsia, intrauterine growth restric- tion, or both and 20 normal pregnancies. The authors found a significant correlation between the RI and both plasma viscosity and gestational age. Further- more, 55% of the variance seen in the RI could be explained by plasma viscosity. The major determinants of fetoplacental flow impedance, however, were peripheral vascular factors, not whole-blood viscosity. It may be concluded, then, that the viscosity of fetal blood need not be considered when interpreting the umbilical arterial Doppler indices.

Maternal Posture and Umbilical Arterial Doppler Indices

Most biophysical fetal surveillance tests, including electronic fetal heart rate monitoring, the biophysical profile examination, and Doppler interrogation of the fetal circulation, are performed with the mother in the semirecumbent position with left lateral tilt so the risk of supine hypotension is minimized. For Doppler testing this protocol is implemented on an empiric basis. The effect of maternal posture on the umbilical arterial Doppler indices, however, has been investigated. Kinsella and coinvestigators [47] as- sessed maternal and fetal cardiovascular effects of position change in 20 women in late pregnancy. On changing from the left lateral to the supine position, there was a 45% reduction in leg blood flow but no changes in femoral, brachial, or uterine arterial resistance as measured with Doppler ultrasonography.

The leg blood pressure also did not change, indicat- ing the absence of significant aortic compression. The maternal heart rate increased in the supine position, however, suggesting the presence of inferior vena caval compression. Notably, the fetal heart rate and umbilical Doppler indices did not vary with maternal postural change. The effect of posture was investigated more extensively by Sorensen and associates [48], who studied the effects of orthostatic stress and maternal hemodynamics on the umbilical arterial S/D ratios in normal and hypertensive pregnancies.

Although all mothers demonstrated a decline in cardiac output and increased total peripheral resistance

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on standing, there was no change in the S/D ratio in normotensive patients when they were moved to the upright position. In contrast, the ratio significantly increased with a postural change in hypertensive patients and was more pronounced with high resistance hypertension.

Maternal Exercise and Umbilical Arterial Doppler Indices

The fetal circulatory response to maternal hemodynamic stress secondary to maternal exercise may be an important consideration when timing a fetal Dop- pler investigation. Several investigators have addressed this issue [49±51]. All of these studies, which employed some form of bicycle ergometry, demonstrated an exercise-induced response in the maternal cardiovascular system. The fetal cardiac chronotropic response was variable. Often the response was tachycardia, although a lack of variation was also noted. Most studies failed to show changes in the umbilical arterial Doppler indices.

When such changes were noted, they were associated with fetal heart rate alterations. From these investigations it appears that mild to moderate exercise does not affect flow impedance in the umbilical artery independent of changes in the fetal heart rate.

Summary

The umbilical arterial circulation is readily accessible to continuous-wave and pulsed-wave Doppler interrogation. The procedure is relatively simple. The variance of umbilical arterial Doppler indices is affected by both hemodynamic and nonhemodynamic factors.

The latter represent the error component of the measurement and are attributable to observer and prob- ably instrumental factors. The hemodynamic factors include physiologic and pathologic phenomena. Of the former, the gestational age, fetal breathing, fetal heart rate, and site of measurement are the most important contributors.

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