Assessment of venous flow in normal and high-risk fetuses: Is the future now?

July 6, 2011

Since the first report of Doppler ultrasound evaluating high-risk pregnancies in 1983, the fetal arterial system has been extensively studied to determine if abnormal waveforms identify fetuses at increased risk for perinatal mortality.

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INTRODUCTION

Since the first report of Doppler ultrasound evaluating high-risk pregnancies in 1983, the fetal arterial system has been extensively studied to determine if abnormal waveforms identify fetuses at increased risk for perinatal mortality 1,2. Recent meta-analysis of randomized controlled trials suggests that incorporation of umbilical artery Doppler waveform analysis into management protocols for high-risk pregnancies significantly decreases perinatal mortality 3,4. Investigators have suggested that the time period between identification of an abnormal umbilical artery Doppler waveform and the development of fetal distress and/or death varies widely - from days to weeks 5,6. Therefore, the challenge is to identify fetuses at greatest risk for adverse perinatal outcome when abnormal umbilical artery waveforms are present. Recent studies have suggested that Doppler evaluation of the venous system may fulfill this role 7-10.

Because the venous system presents imaging challenges and physiological concepts which may not be familiar to all physicians or sonographer who image the fetus, this paper will review:

  • Principles of the pulsed venous Doppler waveform;
  • The use of color and pulsed Doppler ultrasound to identify venous vessels and record the waveforms for analysis;
  • The quantification of normal venous waveforms; and
  • The comparison of arterial and venous waveforms to predict adverse outcome in high-risk fetuses.

THE NORMAL VENOUS WAVEFORM

In the postnatal period, the venous waveform recorded with pulsed Doppler consists of three components:

  • Forward flow during ventricular systole which is in response to the fall in atrial pressure that accompanies atrial relaxation and the downward displacement of the tricuspid or mitral annulus as the right and left ventricles contract;
  • Forward flow during ventricular diastole which is due to the fall in atrial pressure that accompanies ventricular filling; and
  • Retrograde flow resulting from atrial contraction 11.

The waveform described in the adult has also been described in fetal vessels using the experimental animal model as well as the human fetus. 7, 12Figure 1 illustrates the three components of the venous waveform. Measurements can be classified as angle-dependent or angle-independent, depending upon the angle at which the pulsed Doppler sample volume intersects the direction of blood flow 7-10. An angle-dependent measurement requires the Doppler sample volume to be directed no greater than 20o from the direction of blood flow so that accurate Maximal Peak Velocity as well as the Time Averaged Velocity (Tamx) can be recorded (Figure 1). These are important parameters for measuring hemodynamic changes as a function of fetal growth. Angle-independent measurements have been used in equations which involve ratios of peak velocity and/or the Tamx. While this method allows the examiner a wider latitude for placement of the Doppler sample volume, the only limitation is that blood flow not be recorded 90o to the sample volume because it may adversely alter the pulsed Doppler waveform and provide erroneous information. While the literature contains varied terminology for venous measurements, this review will maintain consistent terms and abbreviations so it will be easier for the reader to compare results from different studies(Figure 1).

 

VENOUS ANATOMY AND WAVEFORM ANALYSIS: THE ROLE OF COLOR AND PULSED DOPPLER ULTRASOUND

Blood flowing into the left atrium

Animal studies have suggested that blood from the ductus venosus preferentially enters the left atrium through the foramen ovale, with little or no mixing occurring within the right atrial chamber 13 . This results in streaming of oxygenated blood into the left atrium, avoiding mixing with deoxygenated blood from the right atrial chamber. Kiserud et al recently suggested, however, that there appeared to be controversy in the literature because several investigators have suggested that, in the human fetus, blood first enters the right atrium, and then flows across the foramen ovale to the left atrium 14-16 . In an attempt to clarify this issue, Kiserud et al studied 103 fetuses between 15 and 40 weeks of gestation with color Doppler ultrasound 14. They reported that the segment of the inferior vena cava proximal to the right atrium contained a confluence of ‘right’ and ‘left’ pathways (Figure 2).

 

The right pathway contained blood originating from the inferior and superior vena cava and the right hepatic vein, while blood from the left pathway originated from the ductus venosus and the left hepatic vein. Although both right and left pathways become confluent upon entrance into the terminal portion of the inferior vena cava, Kiserud et al were able to demonstrate preferential streaming, the right pathway directing blood to the right atrium; the left pathway directing blood to the left atrium through the foramen ovale (Figure 3) 14. These observations are consistent with those recently made in the sheep by Schmidt, Silverman, and Rudolph who reported ‘Two blood streams of different flow velocities were identified within the cephalic portion of the inferior vena cava. The stream that originated from the narrowed ductus venosus had a higher velocity than that from the caudal inferior vena cava (mean velocity, 57 +/- 13 versus 16 +/- 3 cm/s; p < .0002). Facilitated by the Eustachian valve and the septum primum, the ductus venosus stream preferentially passed through the foramen ovale to the left atrium. This flow occurred during most of the cardiac cycle, except for 19.6 +/- 2.3% of the cycle when the foramen ovale was closed during atrial contraction’ 17. Given these recent observations, examination of the inferior vena cava and the ductus venosus should occur at specific sites within these vessels, distal from their confluence at the entrance to the right atrium.

 

 

Ductus venosus

The ductus venosus is located at the cephalic end of the intra-abdominal portion of the umbilical vein. Since the ductus venosus is a small vessel measuring only a few millimeters in diameter, it is often difficult to visualize with real-time ultrasound. However, color Doppler ultrasound enables the examiner to rapidly and accurately identify this vessel. The reason for this is because flow through the ductus venosus is accelerated, and, as a consequence of its small size, turbulent. Identification of the ductus venosus can be accomplished using two approaches. First, the examiner directs the ultrasound beam transversely through the fetal abdomen at the level of the stomach. After activating the color Doppler using a low velocity setting (<0.24 m/s), three vessels can be imaged in cross-section: the abdominal aorta, the inferior vena, and the ductus venosus (Figure 4).

In this view the ductus venosus is located to the right of the stomach, in a plane anterior to the abdominal aorta. Because of turbulent flow, the ductus venosus often has a ‘sparkling’ appearance which is the result of aliasing. Once the ductus venosus is identified, the transducer beam is rotated 90o to image the long axis of this vessel which allows the examiner to adjust the angle of the pulsed Doppler sample volume for angle-dependent measurements (Figure 4). Unlike the superior and inferior vena cavae in which there may be reverse flow during atrial systole, flow through the ductus venosus demonstrates continuous forward flow towards the heart. (Figure 4). There are three pulsatile components (ventricular systole, early ventricular diastole, and atrial systole) which occur during the cardiac cycle: (Figure 4).

 

Foramen ovale

It has been estimated that between 17% and 31% of the total cardiac output crosses the foramen ovale 18. Although real-time ultrasound is used to image this structure, color Doppler ultrasound allows the examiner to identify the direction of the blood flowing through the foramen ovale so that the pulsed Doppler sample volume can be properly placed to record the waveform 19. As the result of low-velocity flow through the foramen ovale, the color Doppler velocity setting should be decreased to a level less than that used for imaging the ventricular chambers and the outflow tracts. The pulsed Doppler waveform is obtained by placing the Doppler sample volume lateral to the atrial septum, within the foramen ovale (Figure 5). There are three pulsatile components which occur in the normal waveform during the cardiac cycle: flow into the left atrium during ventricular systole and early ventricular diastole, decreased, absent, or reversed flow during atrial systole (Figure 5) 20, 21.

 

Pulmonary veins

The color Doppler ultrasound identification of the pulmonary veins entering the left atrium was first reported by DeVore in 1992 22. Using a similar technique, Laudy and colleagues in 1995 identified pulmonary veins entering the left atrial chamber and recorded the venous waveform with pulsed Doppler ultrasound23 . They identified three pulsatile forward flow components (ventricular systole, early ventricular diastole, and atrial systole) in the normal waveform which occur during the cardiac cycle (Figure 6) 23.

 

Blood flowing into the right atrium

The inferior vena cava

There are two approaches which can be used to image the inferior vena cava with color Doppler ultrasound to obtain the pulsed Doppler waveform. The first requires the examiner to direct the ultrasound beam transversely through the fetal abdomen at the level of the stomach. After activating the color Doppler using a low velocity setting (<0.24 m/s), three vessels can be imaged in cross-section: the abdominal aorta, the inferior vena, and the ductus venosus (Figure 7). In this view the inferior vena cava is located to the right of the abdominal aorta. The second approach requires the examiner to image the inferior vena cava in the transverse plane as just described, then rotate the transducer beam 90o to image the long axis of the vessel. This allows the examiner to adjust the angle of the pulsed Doppler sample volume for angle dependent measurements (Figure 7). The pulsed Doppler waveform of the inferior vena cava has three components: forward flow during ventricular systole, forward flow during early ventricular diastole; and reverse, absent, or forward flow during atrial systole (Figure 7) 7, 24.

 

Superior vena cava

The superior vena cava enters the cephalic portion of the right atrium and directs blood through the tricuspid valve into the right ventricle. There are two methods used to identify the superior vena cava using the four-chamber view as the reference point. The first requires the examiner to direct the ultrasound beam cephalad, towards the fetal head (Figure 8). The superior vena cava can be identified at the level of the bifurcation of the pulmonary arteries, just above the five-chamber view. In this plane the superior vena cava is located to the right of the ascending aorta (Figure 8). The second method requires the transducer beam to be rotated 90o from the four-chamber view, directing it parallel to the fetal spine (Figure 2). Once this is accomplished, the transducer beam is moved laterally, toward the right side of the fetus. The superior cava is identified as it enters the right atrium (Figure 2). The pulsed Doppler waveform mirrors the inferior vena cava waveform in its shape and has three components: flow towards the right atrium during ventricular systole and early ventricular diastole, and reverse or absent flow during atrial systole (Figure 8) 7.

 

QUANTIFICATION OF VENOUS WAVEFORMS IN NORMAL FETUSES

Blood flowing into the left atrium

Ductus venosus

In 1992 Kiserud and colleagues reported results from examination of 29 normal fetuses and found that the Tamx of the waveform and the peak velocity of at the (A) wave increased linearly with gestational age 25. In 1992, Huisman et al performed a cross-sectional study of 60 fetuses between 19 and 39 weeks of gestation and divided them into three groups: 19-22 weeks, 27-30 weeks, and 36 to 39 weeks 26. They found that the Tamx and the peak velocity of the peak systolic velocity (S) and the peak diastolic (D) waves increased with gestational age, but made no mention of changes in the A wave peak velocity. Huisman and colleagues reported that the ductus venosus had a higher peak velocity (40-80 cm/s) than other venous vessels (inferior vena cava, right hepatic vein and umbilical vein) 26. In 1994, Hecher and colleagues reported results from a cross-sectional study of 134 normal fetuses. The Tamx, S and D peak velocities increased from 18 to 30 weeks did not change from 30 to 34 weeks and then decreased from 34 to 40 weeks. The A wave demonstrated an increase in velocity until 34 weeks, following which it did not increase 24.

In 1993, DeVore and Horenstein studied fetuses between 16 and 30 weeks of gestation and reported the ductus venosus resistance index [(S-A)/S], which was angle independent, and found that the ratio decreased linearly as a function of increasing gestational age [0.755757 - ((0.0125484) (weeks’ gestation)); SD 0.072; r = 0.045; p<0.001] 27. The reason for their findings was the increase in velocity of the A wave associated with increasing gestational age. In 1994, Rizzo and colleagues reported results from 164 normal fetuses studied between 16 and 42 weeks of gestation and found that the angle-independent S/A ratio decreased with gestational age [3.35 - ((0.049) (weeks’ gestation); SD = 0.490; r = 0.474; p < 0.001] 28. This was attributed to an increase in the velocity of the A wave. In 1995 Hecher and co-workers described similar findings, a linear decrease in the peak velocity index for veins (PVIV) and pulsatility index for veins (PIV) which was attributed to an increase of the A wave velocity 24. Although these three studies measured different ratios, all reported a linear decrease of their respective ratios as a function of gestational age. This was attributed to an increase in the A wave peak velocity which resulted in a decrease in the value of the numerator of the equations. This suggested that as the fetus ages, the compliance of the right ventricle increases and/or the ventricle becomes less stiff.

Foramen ovale

Phillipos and colleagues measured the size of the foramen ovale in 100 normal fetuses and interatrial flow patterns in 30 normal fetuses between 20 and 38 weeks of gestation 20. They reported that the diameter of the foramen ovale increased linearly with gestational age. The diameter of the foramen ovale was similar, whether measured with real-time or color Doppler ultrasound. Because of the small sample size, measurements of the pulsed Doppler waveform were not performed.

Pulmonary Vein

In 1995 Laudy and colleagues measured the peak velocity of the S, D, and A waves and computed the S/A ratio 23. They also measured the Tamx for the entire waveform. They found a significant increase of the Tamx, and the S, D, and A peak velocity waveforms with advancing gestational age. The S/D ratio demonstrated a statistically significant decrease with advancing gestational age. 23.

Blood flowing into the right atrium

Inferior vena cava

In 1990 Reed and co-workers published results from a study of 16 normal fetuses in which they measured the peak velocity and the Tamx of the S, D, and A waves (Figure 6) 7 . They reported the S/D ratios of the peak velocity and Tamx decreased with advancing gestational age and found 87% of fetuses demonstrated reverse flow of the A wave 7. Rizzo’s group in 1992 reported results from a cross-sectional study of 118 normal fetuses between 18 and 40 weeks of gestation 8. They measured the peak velocities and the Tamx for the S, D, and A waves (Figure 7). From these measurements, the following were computed: S/D ratio of the peak velocities, the S/D ratio of the Tamx , and the percent of reverse flow occurring during atrial systole [ATamx /(STamx + DTamx)]. They reported no significant increase associated with gestational age for S/D ratios of the peak velocities and the Tamx. However, the percent of reverse flow occurring during atrial systole significantly decreased with gestational age [percentage reverse flow = 24.671 - ((weeks’ gestation) (0.499)); SD = 2.557, r = 0.775, p < 0.001].

Following the report by Rizzo’s group, Hecher group in 1994 reported results from 127 normal fetuses in which the peak velocities of the S, D, and A waves were measured. The computed indices included the Tamx for the entire waveform (S+D+A), the PVIV and the PIV 24. Hecher’s study found that, as the fetus grew, there was an increase in peak velocity of the S and D waveforms, as well as the amount of blood returning to the right atrium, as represented by an increase in the Tamx of the waveform. The decrease in the PVIV and the PIV were the result of a decrease in the peak velocity of the A wave. The decrease in the velocity of the A wave most likely was the result of a decrease in right ventricular afterload and/or an increase in ventricular compliance. Unlike Rizzo’s group, who reported reverse flow of the A wave for all normal fetuses, Hecher and colleagues reported that reverse flow became less frequent as gestational age increased 8,24. Review of Hecher’s graphical data suggested that less than 10% of fetuses had reverse flow of the A wave after 31 weeks of gestation24. The absence of reverse flow of the A wave in all normal fetuses was suggested by Reed and co-workers in their small series, and, more recently in a study by Gudmundsson and colleagues who noted that 37% of normal fetuses had no reversal of the A wave 7,24. After excluding fetuses without reversal of the A wave, Gudmundsson’s group demonstrated a decrease in the percentage of reversal of A wave flow as gestational age increased 29. As the result of this observation, the PIV and PVIV advocated by Hecher and colleagues, may be the most appropriate non-angle dependent method for evaluating venous waveforms since these equations allow for the measurement of forward, reverse, or absent flow during atrial systole 24.

Superior vena cava

In 1990 Reed and colleagues compared the Tamx of the S, D, and A waveforms of the superior and inferior vena cava and found that the S/D ratios were not statistically different between the superior (3.70 + 0.39) and inferior (3.32 + 0.20) vena cava 7. However, the percentage of reverse flow occurring during atrial systole [(ATamx/(STamx + DTamx)] was greater for the inferior vena cava (8.6 + 1.3%) than the superior vena cava (4.9 + 0.7%).

COMPARISON OF ARTERIAL AND VENOUS WAVEFORM ANALYSIS IN HIGH-RISK FETUSES

Although a number of authors have reported abnormal findings of the fetal venous system in high-risk fetuses, this review will focus on studies from Rizzo’s group in Rome, Italy, and Hecher’s group in London, England. Both groups of investigators have simultaneously examined the venous and arterial systems with pulsed Doppler ultrasound in high-risk fetuses. Reviewing data from these groups will allow the reader to integrate information derived from assessment of the arterial and venous systems and provide a clearer perspective as to the significance of the observations.

Rome studies

Inferior vena cava

In 1994 Rizzo and colleagues reported a cross-sectional study of 79 small for gestational age (SGA) fetuses 8. They measured the pulsatility index of the following arterial vessels: umbilical artery, descending aorta, renal artery, internal carotid artery, and the middle cerebral artery. The inferior vena cava waveform was analyzed and the following computed: peak velocity S/D ratio, the Tamx S/D ratio, and the percentage of reverse flow of the A wave [ATamx / (STamx + DTamx)]. The SGA fetuses were divided into three groups based upon the pulsatility index (PI) of the umbilical artery Doppler waveform. The outcomes were compared with fetuses who were appropriate-for-gestational age and had normal umbilical artery pulsed Doppler waveforms.

Group I: SGA fetuses with a normal PI of the umbilical artery Compared to normal fetuses, there were no significant differences for the S/D ratio of the peak velocities, the S/D ratio of Tamx, and the percent of reverse flow occurring during atrial systole.

Group II: SGA fetuses with a PI > 95th centile and end-diastolic velocities Compared to normal fetuses, there was a significant increase in the peak velocity S/D ratio, the S/DTamx ratio, and the percent of reverse flow of the A wave. When SGA fetuses were categorized by the presence or absence of an abnormal percent of reverse flow of the A wave, those with an abnormal ratio had a significantly greater risk for antepartum late heart rate decelerations (78% vs. 33%; p < 0.01), a shorter time interval from diagnosis to delivery (11 days vs. 32 days) and a lower umbilical artery pH (7.181 + 0.022 vs. 7.228 + 0.031, p < 0.001). However, there were no differences in birth weight, or abnormal arterial waveforms between those with normal vs. abnormal inferior vena cava waveforms.

Group III: SGA fetuses with a PI > 95th centile and absent end-diastolic velocities Compared to normal fetuses, the peak velocity S/D ratio, S/DTamx ratio, and the percentage of reverse flow of the A wave were significantly higher. When SGA fetuses were categorized by the presence or absence of abnormal percent of reverse flow of the A wave, the incidence of antepartum late heart rate decelerations was higher (86% vs. 33%; p < 0.03), and the median time from diagnosis to delivery shorter (5 days vs. 26 days). Three of four neonatal deaths occurred in fetuses with an abnormal percentage of reverse flow of the A wave.

Longitudinal study The fetuses in this study were also examined longitudinally. The authors reported that there were minimal to no changes over time in the pulsatility index of the umbilical, middle cerebral, descending aorta, and renal artery. However, there was a significant change in the peak velocity S/D ratio (p < 0.0001), the S/DTamx ratio (p < 0.0001), and the percentage of reverse flow of the A wave (p < 0.001). This suggested that changes in venous flow preceded abnormal outcome when abnormal arterial waveforms were present.

Ductus venosus

In 1994 Rizzo and colleagues reported findings from 97 SGA fetuses who were divided into the same three groups based upon the umbilical artery (UA)/middle cerebral artery (MCA) pulsatility index (PI) ratio. The findings and outcomes were compared with normal fetuses. The S and A peak velocities were measured and the S/A ratio computed.

Group A: SGA fetuses with a normal UA/MCA PI ratio There was no significant difference in the S/A ratio between normal and Group A fetuses.

Group B: SGA fetuses with an UA/MCA PI ratio > 95th centile and end-diastolic flow in the umbilical artery There was a significant difference in the S/A ratio between normal and Group B fetuses. Review of the graphical data suggest that 32% (13 of 41) of these fetuses had an abnormal S/A ratio.

Group C: SGA fetuses with an UA/MCA PI ratio > 95th centile and absent end-diastolic flow in the umbilical artery There was a significant difference in the S/A ratio between normal and Group C fetuses. Review of the graphical data suggest that 78% (18 of 23) fetuses had an abnormal S/A ratio.

When Group B fetuses were analyzed for adverse outcome, those with an abnormal S/A ratio had a shorter interval between diagnosis and delivery (12 days vs. 20 days, p < 0.05), and a lower umbilical artery pH (7.212 + 0.033 vs. 7.247 + 0.041; p < 0.02).

When Group B and C fetuses were combined and analyzed for adverse outcome, those with an S/A ratio greater than the 95th confidence interval had a shorter interval between diagnosis and delivery (6 days vs. 18 days; p < 0.01); a lower umbilical artery pH at birth (7.198 + .023 vs. 7.231 + 0.043; p < 0.001), and a higher perinatal mortality [26% (8/31) vs. 6% (2/33); p < 0.001] . When fetuses in Groups B and C were followed longitudinally, the S/A ratio increased until the onset of late decelerations (p <0.001).

This suggested that, given the abnormal umbilical artery waveforms, changes in the S/A ratio preceded the onset of late decelerations. In addition, given the same degree of growth retardation and abnormal umbilical artery/middle cerebral artery PI ratios, those with an abnormal S/A ratio had a higher rate of perinatal morbidity and mortality.

Prediction of abnormal blood gases

In 1995, Rizzo’s group compared Doppler waveforms obtained from the arterial and the venous circulatory systems to determine which predicted hypoxia and acidosis 30. Forty-eight growth retarded fetuses were examined with Doppler ultrasound prior to cordocentesis. To qualify for the study, the umbilical artery PI had to be greater than the 95th percentile for their population. Pulsed Doppler waveform recordings included the umbilical artery, middle cerebral artery, thoracic descending aorta, renal artery, ascending aorta, pulmonary artery, inferior vena cava, and the ductus venosus . Doppler indices which were computed consisted of the pulsatility index of the umbilical artery, middle cerebral artery, ductus arteriosus, and renal artery; the peak velocity of the aortic and pulmonary outflow tracts; the percentage of reverse flow of the inferior vena cava; and the S/A ratio of the ductus venosus. Using stepwise logistic regression, the authors reported that The PI of the middle cerebral was the best predictors of hypoxemia, while the percent of reverse flow of the inferior vena cava was the best predictor of acidemia and hypercapnia. Following analysis by stepwise logistic regression, the authors examined receiver operator curves and found that using a cut-off value above 2 SD, an abnormal percentage of reverse flow in the inferior vena cava had a sensitivity of 95% and a specificity of 75% in predicting acidosis and a sensitivity of 75% and a specificity of 70% in the prediction of hypercapnia. A middle cerebral artery PI value below 2 SD had a sensitivity of 92% and a specificity of 70% in predicting hypoxemia. The authors suggested that, when evaluating the fetus with intrauterine growth retardation, the clinician should examine the middle cerebral artery to determine if hypoxemia is present and compute the percent of reverse flow for the A wave of the inferior vena cava to determine the risk for acidemia and hypercapnia.

London studies

Inferior vena cava and ductus venosus

In 1995, Hecher and colleagues reported results from 103 high-risk fetuses between 23 and 42 weeks of gestation in which 66% were small for gestational age and 33% were normally growing at the time of the initial ultrasound examination 9. The authors measured the pulsatility index of the umbilical artery, thoracic aorta, and middle cerebral artery; the E/A ratio of the mitral and tricuspid valves; and the PIV and PVIV of the ductus venosus and inferior vena cava.

Assessment of all high-risk fetuses

The high-risk fetuses were categorized by the presence or absence of adverse perinatal outcome which was defined as any of the following:

(1) cesarean section resulting from an abnormal fetal heart rate tracing;

(2) cesarean section for severe preeclampsia, or

(3) intrauterine death within 10 days of the examination.

The Doppler waveforms were compared between high-risk fetuses with normal and adverse outcomes, but not between high-risk fetuses and normal controls.

  • (1) Fetuses < 28 weeks of gestation. The high-risk fetuses with adverse outcome had significant differences in the following: PI of the umbilical artery, thoracic aorta, and middle cerebral artery; E/A ratio of the mitral valve; PVIV of the ductus venosus; PIV of the ductus venosus and the inferior vena cava.

(2) Fetuses > 28 weeks < 32 weeks’ gestation Fetuses with adverse outcome demonstrated significant differences in the following: PI of the umbilical artery, thoracic aorta, and middle cerebral artery; PVIV of the ductus venosus and inferior vena cava; and PIV of the ductus venosus and the inferior vena cava. Unlike fetuses less than 28 weeks of gestation, there was no significant difference in the E/A ratio of the mitral valve. In addition, the PVIV for the ductus venosus was abnormal at this gestational age, but not in fetuses less than 28 weeks of gestation.

(3) Fetuses > 32 weeks’ gestation Fetuses with adverse outcome demonstrated significant differences in the following: PI of the umbilical artery, thoracic aorta, and middle cerebral artery; and PVIV and PIV of the inferior vena cava. Unlike fetuses less than 28 weeks of gestation, there was no significant difference in the E/A ratio of the mitral valve. In addition, the PVIV and PIV for the ductus venosus was not abnormal at this gestational age, as it was in the lower age groups.

These findings would suggest that there is a differential manifestation of abnormal venous waveforms in high-risk fetuses which is gestational-age dependent. For this reason, if an examiner were to measure only one venous waveform, the choice would be the inferior vena cava PIV [(S-A)/Tamx]. If, however, the fetus was less than 32 weeks of gestation, then the ductus venosus PIV could be used.

Assessment of fetuses with abnormal arterial redistribution A subgroup of fetuses in the study were identified in which an abnormal umbilical artery PI and abnormal PI of middle cerebral artery were present, suggesting redistribution of blood flow to the brain. The following abnormal outcomes were examined:

  • (1) Abnormal non-stress test Fetuses with an abnormal non-stress test demonstrated significant differences in the following: PI of the umbilical artery, PI of the thoracic aorta, PIV and PVIV of the inferior vena cava and ductus venosus.

(2) Abnormal biophysical profile Fetuses with an abnormal biophysical profile demonstrated significant differences in the following: PI of the umbilical artery, PIV of the inferior vena cava and ductus venosus; and PVIV of the ductus venosus.

(3) Cesarean section for fetal distress or intrauterine death Fetuses in this group had a significantly higher PIV and PVIV of the inferior vena cava and the ductus venosus. However, there was no significant differences between the arterial and cardiac measurements.

This subgroup illustrates that, in the most compromised fetuses, as defined by redistribution of blood flow to the fetal head, only assessment of the PIV and PVIV of the inferior vena cava and the ductus venosus predicted adverse outcome. These data would confirm the observations of Rizzo and colleagues that changes in the venous system precede adverse perinatal outcome once abnormalities of the arterial system have occurred 8, 28, 30 .

Prediction of abnormal blood gases

In 1995, Hecher and colleagues reported findings from 23 severely growth-retarded fetuses undergoing cordocentesis in which blood gas results were correlated with Doppler waveform analysis obtained from the descending thoracic aorta, middle cerebral artery, inferior vena cava, ductus venosus, and atrioventricular valves 31. Multiple regression analysis demonstrated that the PI ratio (thoracic aorta PI /middle cerebral artery PI) and the ductus venosus PIV [(S-A)/Tamx] provided independent information on the degree of acidemia. From this data set, they found a significant correlation in the observed and predicted delta pH using the following equation: delta pH = -1.696 - 0.331 (thoracic aorta PI/middle cerebral artery PI) - 0.292 (ductus venosus PIV); r = 0.681, p < 0.001. They found no associations between the percent of reverse flow in the inferior vena cava and abnormal blood gases.

COMMENTS

The studies reviewed for this article would suggest that abnormalities of the venous waveform precede significant adverse perinatal outcome. Of the various components which can be measured, those that reflect changes in the A wave appear to be the best predictors of adverse outcome. The A wave reflects the simultaneous hemodynamic state of the venous reservoir of blood awaiting return to the heart, the pressure and contractility of the right atrium, and the compliance or ‘stiffness’ of the right ventricle. In animal and adult studies, investigators have found that as the myocardium became hypoxic, the amount retrograde flow of A wave increased 12, 32. It was postulated that hypoxia may have resulted in a less compliant, or ‘stiffer’ right ventricle which would result in greater resistance to flow from the right atrial chamber to the right ventricle during atrial systole. While the effect of altered compliance or increased ‘stiffness’ is not possible to measure non-invasively in the human fetus, there are pathological models which may help to understand this phenomena. DeVore and Horenstein reported in 1993 that the A wave of the ductus venosus was absent or reversed when measured in a fetus with tricuspid atresia, but normal in a fetus with a hypoplastic left ventricle27. This observation supports the concept that, during atrial systole, the A wave of the ductus venosus reflects the hemodynamic status of the right ventricle, since the foramen ovale is closed during atrial systole. The pathological A wave observed when tricuspid atresia was present was identical to observations in the hypoxic or acidotic fetus discussed in the current review. A second model reflecting ventricular ‘stiffness’ is present in the fetus without structural malformations of the heart. Examination of the inferior vena cava, ductus venosus, and the umbilical vein in the first trimester fetus demonstrates venous waveforms which are equivalent to the most severe abnormal waveforms associated with adverse outcome in the late second and third trimesters of pregnancy 33, 34. It has long been appreciated that the fetal heart muscle is less compliant than the adult heart muscle. As the fetus ages, the heart muscle becomes less stiff, or more compliant. This would suggest that fetal venous waveforms in the compromised late second and third trimester fetus to those observed in the embryonic period, when the fetal heart muscle is the least compliant.

While a large amount of work has already been done by many investigators, there are still questions that need to be addressed. These include the following:

  • (1) Since the superior vena cava reflects flow directed into the right ventricle which does not mix with flow from the ductus venosus and hepatic veins, would the superior vena cava provide more information relating to right ventricular function than the inferior vena cava or the ductus venosus?

(2) Although the studies reviewed in this paper have focused primarily on right heart hemodynamics, could left ventricular function be more predictive of adverse outcome than right ventricular function? Studies of the pulmonary vein in high-risk fetuses could answer this question and offer more insight into hemodynamic changes associated with adverse outcome.

(3) The studies reviewed for this article have focused on pulsed Doppler measurements of the heart, arterial, and the venous systems. No mention has been made regarding the size, shape, or contractility of the atrial or ventricular chambers. Could the real-time four-chamber view provide valuable screening information in high-risk fetuses?

4. Although the venous system has been examined in high-risk fetuses, most of which had severe intrauterine growth retardation, what occurs in the non-growth retarded fetus who develops late third trimester growth failure, oligohydramnios, and/or fetal distress in labor?

Perhaps it is time to reflect on our choice of tests for fetal antepartum surveillance. Although the non-stress test, biophysical profile, and the amniotic fluid index are widely used, it is important to remember that the evidence for their effectiveness are derived from uncontrolled observations. The only fetal surveillance test that has been proven to decrease perinatal morbidity and mortality is Doppler velocimetry of the umbilical artery. Meta-analysis of randomized clinical trials has demonstrated the effectiveness of this test 3,4. The next step is to determine if expanding the study of fetal cardiovascular hemodynamics will add to the knowledge provided by examination of the umbilical artery. The studies reviewed in this paper would suggest such an advantage. As additional information becomes available confirming the observations of the authors who were the subject of this review, the physician who cares for the high-risk fetus should be prepared to image the cardiovascular and venous systems and interpret the information for clinical management. Depending upon how rapidly this occurs, the future may soon be upon us!

References:

REFERENCES

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