This chapter focuses on the Doppler interrogation of the fetal circulation. Other chapters in this book focus on Doppler velocimetry of the uterine arteries and fetal echocardiography. Randomized clinical trials have demonstrated that Doppler examination of the umbilical arteries can reduce perinatal mortality. Therefore, practitioners need to be familiar with the sampling, interpretation, and clinical significance of these vessels. Similarly, Doppler examination of the venous system (ductus venosus, inferior vena cava [IVC], and umbilical vein) are informative of cardiac function and identify a fetus at risk for impending in utero death. Finally, examination of the peak systolic velocity of the middle cerebral artery has become important in the assessment of fetal anemia. This chapter reviews the anatomy, physiology, Doppler waveform morphology, normal ranges, and interpretation of an abnormal waveform in clinical practice.

Umbilical artery Doppler velocimetry (UADV) has become an important clinical tool in obstetrical practice. UADV examines the impedance to blood flow in the placenta and therefore is a test of the placental stages. The umbilical arteries are easy to sample because they are long, nonbranching, and surrounded by amniotic fluid.

Anatomy of the Umbilical Arteries

The umbilical arteries are branches of the internal iliac artery that have a pelvic segment around the fetal bladder (Figure 12-1). Thereafter, the umbilical arteries have an upward trajectory inside the fetal abdomen as they travel to the umbilicus to become part of the umbilical cord. The vessels travel in the umbilical cord until the insertion of the placenta. An anastomosis of the umbilical arteries located approximately 3 cm from the placental insertion, acting as a pressure-equalizing system between umbilical arteries, can be demonstrated with ultrasound and is called “Hyrtl anastomosis.”^1,2

The umbilical cord contains 2 arteries and 1 vein. The arteries carry deoxygenated blood from the fetus to the placenta. Such blood is enriched with oxygen in the villous tree and then returns to the fetus through the umbilical vein. Therefore, the umbilical arteries contain blood with a lower PO₂ and pH than that in the umbilical vein.

Physiology of the Umbilical Arteries

The umbilical circulation is a low-resistance vascular bed. Blood flow to the placenta increases with advancing gestational age; this is accomplished by a decrease in vascular resistance of the placenta. Umbilical vessels and placental vessels lack innervation, and they do not respond to vasoconstrictors.

Sampling Techniques

Doppler signals can be obtained in any segment that is visible: around the fetal bladder, in the abdominal insertion of the umbilical cord, in a free loop, or in the placental insertion of the umbilical cord. There is evidence that Doppler indices vary depending upon where the Doppler signal is obtained.^3-6 In general, Doppler indices are higher in the abdominal insertion of the umbilical cord than in the placental insertion.^5,6 Although the difference is not large, a standard recommendation is that the same site be used for sampling, in particular when serial studies are being performed in a fetus at risk.

In most cases, Doppler signals are obtained from a free loop of the umbilical cord because of the ease of acquisition. The placental insertion and the abdominal insertion have the disadvantages of depending upon location. The umbilical arteries can be reliably identified and sampled on both sides of the bladder. This allows exclusion of a single umbilical artery (Figure 12-2) and also standardization. However, because this requires a greater level of skill, the free loop continues to be used in practice.

We obtain Doppler waveforms for analysis by placing the sample volume of a pulsed Doppler system in a manner that would include 1 umbilical artery and 1 vein. However, when there is absence of end-diastolic velocities, we prefer to sample the umbilical artery alone to avoid missing reversal of flow.⁷

The number of waveforms to be obtained has been recommended to vary from 3 to 5.^8-10 It is important to note that the waveforms should be regular to obtain an accurate assessment of the vascular impedance to flow. Ideally, these waveforms should be obtained when the fetus is not breathing and not moving. Fetal breathing can cause changes in the waveform (Figure 12-3).¹⁰ Similarly, an irregular fetal heart rate can also generate artifactual Doppler signals.^11,12

Most clinicians now use the Pulsatility Index (PI) to analyze waveforms. The initial studies employed the S/D ratio because it was easy to calculate (did not require integration of the entire waveform), but this issue has now been solved with modern ultrasound equipment. One advantage of using the PI is that it can be calculated when there are absent end-diastolic velocities. Under such circumstances, neither the S/D ratio nor the Resistivity Index (RI) can be calculated.

Morphology of the Umbilical Artery Waveform and Changes with Gestational Age

In early pregnancy, an absent end-diastolic velocity is a normal finding (Figures 12-4A and B);^13,14 however, the presence of end-diastolic velocities is expected after 18 weeks of gestation.¹⁵ From this point onward the umbilical artery waveform is characterized by forward flow during the entire cardiac cycle. Moreover, end-diastolic velocities are high, and this is consistent with low resistance to flow.^16,17

The placenta increases in size with advancing gestational age, and this is associated with an increased number of tertiary stem villi. As the placenta grows, the vascular resistance decreases. Therefore, the Doppler indices decrease as gestation progresses.¹⁵ This is demonstrated in Figure 12-5 and in Table 12-1, which display the normal values for the PI of the umbilical artery.¹⁸ Longitudinal reference ranges are also available for the blood velocity and PI at the intraabdominal portion and fetal and placental ends of the umbilical artery.⁶

The Physiologic Significance of an Abnormal Umbilical Artery Waveform

Mathematical modeling of the placental circulation indicates that 50% to 60% of terminal arterial vessels must be obliterated for the PI to increase beyond its normal range. It is interesting that there is a steep increase of the PI after 80% of fractional terminal vessels are obliterated.³⁸ Therefore, an abnormal umbilical artery velocimetry reflects substantial pathology of the placental vascular territory. It is noteworthy, according to the results of mathematical modeling, that the same rate of obliteration of the vessels has a stronger effect on the PI in a smaller placenta than in a larger placenta. The effect of obliteration appears to be greater in early gestation when the placenta is smaller, rather than in the third trimester when the placenta is larger.¹⁹

Patients with high Doppler indices have a significantly lower modal number of arterioles in the tertiary stem villi than that in a normal control group (7 to 8 arteries per field in the control group and 1 to 2 arteries per high-power field in the abnormal Doppler group). The pathologic lesion considered to be responsible for this is vascular sclerosis with obliteration of the small muscular arteries of the tertiary stem villi.^39-41 Other vascular lesions associated with abnormal Doppler velocimetry of the umbilical arteries include fetal thrombotic vasculopathy, chronic villitis, and fetal vascular necrosis.^23,24 It is important to note that an abnormal umbilical artery Doppler waveform reflects placental disease and not fetal disease.

Clinical Correlations of Abnormal Umbilical Artery Doppler Velocimetry

Pregnancies with abnormal umbilical artery Doppler velocimetry are at increased risk for (1) perinatal death, (2) small for gestational age (SGA), (3) congenital anomalies, and (4) admission to a neonatal intensive care unit. These conclusions are based on the pioneering and classic studies of Professor Trudinger in a large number of patients who had umbilical artery Doppler velocimetry because they were at risk for adverse pregnancy outcome based upon clinical indications or assessment.^7,31

Meta-analysis of randomized clinical trials in which UADV was used for the management of patients has indicated that the use of this tool results in a reduction of perinatal morbidity of approximately 38%. It is clinically indicated when the diagnosis of SGA is made, there is a history of a fetal demise, or there are obstetrical or medical complications that increase the risk of perinatal morbidity and mortality, such as preeclampsia, chronic hypertension, thrombophilic states, lupus, and other complications of pregnancy.^31-35

Small for Gestational Age

UADV is performed serially in SGA fetuses. Abnormalities of the umbilical artery waveform reflect the presence of placental rather than fetal disease. Therefore, absence or reversal of flow during the diastolic period is not by itself an indication for delivery, but rather an indication for increased surveillance to prevent in utero death.

The spectrum of abnormalities detectable in the waveforms evolves from a progressive reduction in the end-diastolic velocities (reflected by an elevated PI for gestational age), followed by the absence of the end-diastolic flow (AEDF) and, in extreme cases, the occurrence of reverse end-diastolic flow (REDF).^36-40

There is an association between abnormalities of UADV and the fetal acid–base status (lower pH, lower PO₂, acidemia).^41-48 When there is an umbilical artery PI greater than 1.5, lactate concentrations in umbilical venous blood increase sharply.⁴⁷ Moreover, SGA fetuses with abnormal UADV are more likely to experience fetal distress,^49,50 longer neonatal intensive care unit stays, and have a higher perinatal mortality.^31,50-52 An abnormal UADV precedes the development of an abnormal fetal heart tracing by 2 to 4 weeks.^51,54

Congenital/Chromosomal Anomalies

Abnormalities in the UADV in fetuses who are not SGA should raise the suspicion of whether or not there is an undetected fetal congenital anomaly (anatomical or chromosomal).⁵⁵ The spectrum of abnormalities described in association with abnormal umbilical artery Doppler indices is wide. The tertiary villi of placentas from fetuses with karyotype abnormalities often display a reduction in the total vessel count, in the small muscular artery number, and in the small muscular artery to villus ratio.⁵⁶ This under-vascularization may represent placental immaturity as a result of arrested or delayed angiopoiesis⁵⁶ and may predispose to the Doppler abnormalities in the umbilical artery.^57-59

Anatomy of the Umbilical Vein

The umbilical vein carries oxygenated blood from the placenta to the fetus. Its oxygen saturation is the highest in the entire fetal circulation because oxygen extraction by fetal tissues has not yet occurred. The umbilical vein is the longest vessel in the human fetus. Its diameter, in the free-floating portion, decreases progressively from the fetus to the placenta.⁶⁴ The vessel travels within the umbilical cord in the opposite direction of the 2 umbilical arteries, and after entrance into the abdomen, it courses toward the liver and enters the organ. The vein branches into 2 vessels. The larger joins the portal vein, and together they enter the right lobe of the liver. The smaller vessel, the ductus venosus, carries oxygenated blood into the right atrium and is then shunted into the left atrium (Figure 12-6). In the newborn, the umbilical vein remains patent after birth for a few months. Closure of the umbilical vein usually occurs after closure of the umbilical arteries. After closure, it becomes the ligamentum teres, which is a fibrous cord extending from the umbilicus to the transverse fissure of the liver. There, it joins with the ligamentum venosus, which separates the left and right lobes of the liver.

Sampling Techniques

Doppler interrogation of the umbilical vein can be achieved in a free-floating loop or in various segments of its intraabdominal portion. We usually sample the vessel in a free-floating central part of the cord, recording spectral Doppler signals from the umbilical vein and the artery (arteries) simultaneously.

Morphology of the Umbilical Vein Waveform and Changes with Gestational Age

Under normal circumstances, the velocity flow waveform has a nonpulsatile pattern. Reference ranges are available for the umbilical vein maximum velocity (V_max), time-averaged intensity-weighted mean velocity (V_wmean), and umbilical vein blood flow, based on longitudinal data.⁶ Reference ranges for umbilical vein blood flow, based on cross-sectional data, are also available.⁶⁵ The mean velocity in the umbilical vein is constant between 37 and 40 weeks’ gestation (18.3 ± 4.0 cm/s). At this gestational age, the diameter of the vessel ranges between 5 and 7 mm.⁶⁵

Definition of Umbilical Vein Pulsations

There is no agreement about the definition of umbilical vein pulsations; however, in most studies pulsations are considered to be present based on visual assessment of transient negative deflections of the venous flow velocity waveform (without a need to go below the baseline), in synchrony with the cardiac cycle (Figure 12-7).

Nakai et al⁶⁶ proposed pulsations to be diagnosed when the inflections are detected for more than 10 seconds and in more than 3 sampling sites. According to van Splunder et al,⁶⁷ a deflection in velocity can be defined as a pulsation only if it is greater than at least 10% of the time-averaged velocity. Other authors have proposed a threshold of greater than 15% in the magnitude of the reduction of the blood velocity as a reasonable cutoff.^68,69 It is possible to quantitate the magnitude of the pulsation by calculating the difference between the maximum velocity and the minimum velocity during the pulsation, expressed in centimeters per second.⁷⁰

Three types of umbilical vein pulsations have been recognized: (1) monophasic/single pulsations, in which there is 1 deflection per cardiac cycle (this represents the majority of umbilical vein pulsations); (2) biphasic/double¹⁰⁰ pulsations, in which there are 2 deflections per cardiac cycle, corresponding to systolic and diastolic peaks; and (3) triphasic pulsations,⁷¹ with a positive systolic peak, a positive diastolic peak, and a reverse flow during atrial contraction. Triphasic pulsations have the worst prognosis and have been sporadically described.

Umbilical Vein Pulsations in Normal Pregnancies

Umbilical vein pulsations are physiologically present in the first trimester, but they disappear between 12 and 15 weeks of gestation.^72,73 This is considered to represent reduced conduction of the changes in intracardiac pressures due to a growing umbilical vein.⁷³

Transient umbilical vein pulsations can be present in normal fetuses throughout gestation.⁷⁴ Their frequency changes with gestational age (30% between 13 and 14 weeks, 5.5% at 23 to 24 weeks, and then 5% to 7.8% throughout the rest of pregnancy).⁶⁶

The criteria for a nonpathologic umbilical venous pulsation occurring in a fetus with a normal PI of the umbilical artery are the following: (1) monophasic in nature; (2) an amplitude within one-third of the maximum Doppler shift; (3) detectable only in one or two of all sampling sites; and (4) transient in nature (in other words, not observed in a subsequent examination after an interval of at least 2 weeks).⁶⁶

Pathophysiology of Umbilical Vein Pulsations

Pulsations in the central veins are due to backward transmission of pulses, which occurs to some extent in the normal circulation.⁷⁵ Atrial contraction and relaxation are responsible for the pulsatile flow patterns of the ductus venosus and the IVC. However, these pulsations are not normally transmitted to the umbilical vein after the first trimester.

It is possible that pulsations in the venous system farther from the heart, such as the umbilical vein, are caused by the same mechanism of transmission as those in veins which are close to the heart.⁷⁵ An enhanced atrial contraction, reflecting increased afterload, increased intraatrial pressure, and adrenergic drive,^76,77 may be transmitted to the IVC, the distended ductus venosus, and finally to the umbilical vein.^78,79 The ductus venosus plays a role in the transmission of pulsations to the umbilical vein. A mathematical model has demonstrated that the amplitude of the umbilical vein pulsations depends on the impedance ratio between the umbilical vein and the ductus venosus, as well as on the ratio of the mean velocity and the pulsed wave velocity in the ductus venosus.⁸⁰ Moreover, agenesis of the ductus venosus prevents the transmission of central venous pulsations to the umbilical vein.⁷⁸ This suggests that the appearance of pulsations in the umbilical vein reflects a hemodynamic change, which is transmitted from the right atrium.

The incidence of umbilical venous pulsations is higher at the umbilical ring in the abdominal wall, where the compliance is lower, than in the cord or intraabdominally.⁷⁰

In fetal lambs, umbilical vein pulsations may be obtained by cord occlusion or experimentally induced hypoxia.^77,81,82

Clinical Correlations of Umbilical Vein Pulsations

Although umbilical vein pulsations have been described after 13 weeks in normal fetuses,⁶⁶ their presence after this gestational age should raise suspicion of cardiac failure.^83-86 Some of the conditions in which umbilical vein pulsations have been reported include (1) fetal cardiac dysfunction,^76,87 (2) malformations and chromosomal aberrations,⁸⁸ (3) atrioventricular anomalies,¹⁰³ (4) severe bradycardia and tachycardia,¹¹⁸ (5) nonimmune hydrops,^83,89 and (6) a hypercoiled cord.⁹⁰

Umbilical Vein Pulsations in SGA Fetuses

Umbilical vein pulsations can be detected in advanced stages of intrauterine growth restriction, and are usually associated with severe abnormalities in the umbilical artery and ductus venosus (absent or reverse end-diastolic flow) Doppler velocimetry. Pulsations in the umbilical vein have a high positive predictive value for the identification of the fetus with acidemia,^91,92 at risk for in utero death,⁹¹ birth asphyxia,⁹¹ and neonatal death.⁹¹ Double pulsations in the umbilical vein, combined with absent or reverse end-diastolic flow in the umbilical artery, reflect impaired myocardial function and advanced decompensation of cardiac function.⁶⁸

Adequate cerebral perfusion is required for intact survival. Insults that affect fetal growth, such as placental disease (defined as “absent/reverse end-diastolic velocities” of the umbilical arteries), result in changes in perfusion of the cerebral arteries. The conventional wisdom is that these changes can be demonstrated in the middle cerebral artery (MCA) and anterior cerebral artery, and that they consist in vasodilatation to maintain perfusion to the fetal brain. Consequently, Doppler interrogation of the MCA has become common in obstetrical practice. Recent observations suggest that changes in the anterior cerebral artery may occur before changes in the MCA and that they may have functional consequences in terms of neurological handicap.

Middle Cerebral Artery

Anatomy of the Middle Cerebral Artery

The MCA is a prominent branch of the circle of Willis (Figure 12-8). The arteries of the circle of Willis can be easily imaged with color Doppler mapping (Figures 12-9 and 12-10). The MCA has been divided into 4 segments: M1, M2, M3, and M4. The M1 segment is the most proximal to the circle of Willis and is located before the MCA bifurcation or trifurcation (Figure 12-11). This segment has a diameter that remains relatively constant in physiological and pathological conditions and is where most Doppler interrogation has been conducted. The MCA travels horizontally resting on the sphenoid wings on the base of the skull, and then curves upward and travels within the sylvian fissure. Its branches supply about 80% of the blood flow to the cerebral hemispheres (most of the lateral surface with exclusion of the superior part of the frontal and parietal lobes and the inferior part of the temporal lobe).⁹³ Importantly, the MCA contributes to the blood supply of the internal capsule and the basal ganglia (caudate and globus pallidus).

Sampling Techniques

Doppler interrogation of the MCA is optimally performed in an axial section of the fetal brain. Imaging can be accomplished in the plane of the biparietal diameter and moving toward the base of the skull. The MCA can be visualized even without Doppler, but color flow aids in sampling (Figure 12-12). Many investigators^93-95 prefer to sample the MCA in the near field and in its proximal segment (M1), approximately 2 mm after its origin. In this site, the intra- and interobserver variability is the lowest. Moreover, Doppler indices are less susceptible to the effects of fetal behavioral states than those obtained by recording in the distal segment of the vessel. Standardization of the sampling site is important because there are significant differences in blood flow velocity and vascular impedance between the proximal and distal segments of the MCA (lower PI in the proximal segment than in the distal third of the MCA).^96-98 The far-field proximal site is the best alternative when the near-field proximal site cannot be interrogated.⁹⁸

Two Doppler parameters are important: the MCA PI and the peak systolic velocity. The first is used to detect changes in vasodilatation in fetuses with placental disease and/or SGA. Peak systolic velocities are used in the diagnosis of fetal anemia.

A key consideration in obtaining reliable peak systolic velocity determinations is that the angle of insonation should be 0 degrees or as close to 0 degrees as possible. Small changes in the angle can introduce errors that can affect the estimation of the velocity and have implications for clinical management.¹³² Moreover, the reproducibility of peak systolic velocities is lower with the use of angle correction (higher interobserver variability). It has been recommended that the MCA be magnified prior to sampling so that it occupies more than 50% of the image.

Doppler interrogation should be conducted in the absence of fetal breathing or movements and over at least 3 to 5 uniform cardiac cycles. A pitfall in interrogating the MCA is placing an excessive amount of pressure on the fetal head with the transducer. This may result in increased impedance to flow and artifactual absence of end-diastolic velocities (Figure 12-13).¹⁰⁰

Morphology of the Middle Cerebral Artery Waveform and Changes with Gestational Age

The MCA can be recognized using transvaginal sonography as early as the 10th week of gestation. End-diastolic velocities may be physiologically absent until the 11th week, inconsistently present between the 11th and 13th weeks, but consistently present thereafter.¹⁰¹ The MCA has forward flow during the entire cardiac cycle, and the morphology of the waveform changes with gestational age.¹⁰²

Indices

Tables 12-2 and 12-3 and Figures 12-14 and 12-15 provide longitudinal reference ranges for the MCA peak systolic velocity and for the MCA PI as a function of gestational age. Other reference ranges are available elsewhere.^{97,99,102-108}

Cerebroplacental Doppler Ratio

The ratio of the PI of the MCA divided by the PI of the umbilical artery is known as the cerebroplacental Doppler ratio.¹⁰⁹ This ratio has the advantages of not being heart rate dependent (like the resistance indices) and of providing information about both placental and fetal circulations.

In normal pregnancies, the cerebral (MCA) PI is higher than the umbilical artery PI; therefore, the cerebroplacental ratio is always greater than 1. With advancing gestational age, the ratio first increases (21 weeks: mean = 1.41), reaches a peak (33 weeks: mean = 2.36), and subsequently decreases again (39 weeks: mean = 1.97) (Table 12-4). Cross-sectional reference ranges for Doppler indices for this ratio are also available.^110-112

A low cerebroplacental ratio reflects a redistribution of the cardiac output to the cerebral circulation, which occurs as a fetal adaptation to placental disease (“brain-sparing effect”). The sensitivity of this ratio in the prediction of poor perinatal outcome among SGA fetuses is 90%, compared with 78% of the MCA and 83% for the umbilical artery Doppler waveform indices.¹¹⁰ Moreover, this ratio has been claimed to be more accurate in the prediction of adverse outcome than the MCA or UA Doppler alone.^{110, 113}

The MCA/UA PI ratio can be plotted against gestational age-specific reference ranges.^111,112 However, a threshold of 1.08 is generally used as an indicator of risk. Above this cutoff, cerebral placental circulation is considered normal, and below this cutoff it is abnormal and deserving of careful surveillance.^110,114 The inverse ratio (UA-PI to MCA-PI) has also been used by other investigators, and normal values are available for interpretation of this index.¹¹⁵

Clinical Correlations of an Abnormal Middle Cerebral Artery Doppler Velocimetry

Small for Gestational Age

The increased impedance to flow in the uteroplacental vessels of fetuses with severe intrauterine growth restriction may cause hypoxemia, which induces adaptive responses in the fetal circulation to preserve adequate oxygen supply to the brain, the coronary circulation, and the adrenals.

Brain perfusion in the context of placental disease and chronic hypoxemia is maintained through adaptive hemodynamic changes, which are collectively referred to as the brain-sparing effect. Redistribution of the blood flow to the brain is accomplished by vasoconstriction in the peripheral vessels (ie, descending aorta, renal arteries), and vasodilatation of the MCA, which is detected as a decreased PI in this vessel.

Fetuses with a decreased PI in the MCA are at increased risk of having nonreassuring fetal heart rate patterns and being admitted to the neonatal intensive care unit, and they have almost a 3-fold higher risk of intrauterine death than SGA fetuses with a normal PI of the MCA.¹¹⁶

Longitudinal observations in fetuses with brain-sparing effects show that the nadir of vasodilatation of the MCA is reached 2 weeks before the onset of antepartum late decelerations.¹¹⁷ In severely growth-retarded fetuses, there is an association between Doppler indices of the MCA and fetal blood PO₂.^118,119 The degree of vasodilatation in the MCA correlates with the degree of fetal hypoxemia; however, when the fetal PO₂ falls 2 to 4 SD below the normal for gestation, the maximum reduction of PI is reached and there is a tendency for the PI to rise.⁹⁴ This has been attributed either to cerebral edema⁹⁴ or to a decreased cardiac output in these fetuses.^120,121 Disappearance of cerebral vasodilatation with normalization of a low PI of the MCA is a sign of danger, and we have observed it before fetal death or the development of abnormal fetal heart rate tracing.^115,123,124 Prolonged reverse end-diastolic velocities in the MCA is an agonal pattern.^125,126

Fetal Anemia

Anemia decreases blood viscosity and increases cardiac output. This hemodynamic phenomenon is the basis for the prenatal diagnosis of fetal anemia by measuring the peak systolic velocity in the MCA. There is an inverse correlation between fetal hemoglobin and the peak systolic velocity of the middle cerebral artery (MCA–PSV).^{99,105,127,128} The strength of the correlation increases with the severity of the anemia.¹²⁹ Therefore, the peak systolic velocity of the MCA has become the method of choice to diagnose, noninvasively, the presence of moderate to severe anemia.^99,130 The optimal (100% detection of moderate and severe anemia) threshold values for peak systolic velocity in the MCA in the prediction of fetal anemia were established to be (1) 1.29 times the median for mild anemia, (2) 1.50 times the median for moderate anemia, and (3) 1.55 times the median for severe anemia. After 35 weeks of gestation, the MCA peak systolic velocity has limited value in the diagnosis of fetal anemia, though the reasons for this are not clear.⁹⁹ Differences in compliance of the vessel may contribute to reducing the diagnostic value of this parameter.⁹⁹

Peak systolic velocity of the MCA has also been used for the evaluation of fetal anemia due to Rh-alloimmunization and congenital parvovirus infection,^128,131 and in twin-to-twin transfusion syndrome.¹³² The MCA–PSV is more sensitive and accurate than measurements of amniotic fluid change in optical density at a wavelength of 450 nm.¹³⁰

Anatomy of the Anterior Cerebral Artery

The anterior cerebral arteries (ACAs) are part of the circle of Willis (see Figure 12-8) and are connected to each other by the anterior communicating artery. The ACA supplies most of the medial surface of the cerebral cortex (frontal and parietal lobes), part of the lateral surface of the frontal and parietal lobes (approximately 1 inch), the olfactory bulb and tract, and the anterior four-fifths of the corpus callosum. In addition, perforating branches (including the recurrent artery of Heubner and medial lenticulostriate arteries) supply the anterior limb of the internal capsule and part of the basal ganglia (part of the caudate and globus pallidus). The pericallosal artery is a branch of the anterior cerebral artery.

Sampling Techniques

The appropriate plane to interrogate the ACA is an axial view of the fetal head at the level of the cerebral peduncles, the same anatomical plane as that used to acquire Doppler signals from the MCA.^133,134 An alternative is a coronal plane of the fetal head. In this plane, the pericallosal artery can be visualized traveling cranial to the ACA and with blood flow in the opposite direction.¹³⁵ In the axial plane, sampling after the origin of the ACA from the internal carotid yields better reproducibility than sampling in distal segments after the junction to the anterior communicating artery.¹³⁶ An angle of insonation less than 60 degrees has been considered acceptable.¹³⁴ Flow velocity waveforms in the ACA can be obtained in 64% to 87.5% of cases.¹³⁷ The Doppler signal of the ACA can be weaker than that of the MCA; therefore, optimal flow velocities can be more difficult to obtain (Figure 12-16).¹³⁴

Indices

Reference ranges for the PI of the ACA are available in Figure 12-17.^134,136

Clinical Correlations of an Abnormal Anterior Cerebral Artery Doppler Velocimetry

All four major cranial arteries (ACA, MCA, posterior cerebral artery [PCA], and internal carotid) undergo vasodilatation in the presence of chronic hypoxia, and therefore their PI lowers in cases of severe placental dysfunction (absent reverse end-diastolic velocity of the umbilical artery).¹³⁷

The hemodynamic changes in the cerebral circulation occur with a sequential temporal pattern, suggesting the existence of a hierarchy of different areas of the brain, with preferential and longer sparing of those areas required for long-term survival.¹³⁵

In a substantial proportion of fetuses, the ACA Doppler velocimetry shows significantly lower PI values before abnormalities in the MCA and the PCAs become detectable.^{133,135,168,170,173} This may suggest that, in the presence of chronic hypoxia and cerebral blood flow redistribution, perfusion of the frontal lobes is preferentially preserved.¹³³

In SGA fetuses with abnormalities in UADV, abnormalities in the ACA have similar sensitivity but higher positive predictive value than abnormalities in the MCA in the prediction of adverse perinatal outcome and perinatal mortality.¹³³ Doppler interrogation of the ACA also has prognostic value in monitoring SGA fetuses with normal UADV. Recent studies suggest that the PI of the ACA is a better predictor of adverse perinatal outcome than that of the MCA (at a cutoff value set at the first tertile for gestational age for both ACA-PI and MCA-PI). Sensitivity and specificity of the ACA-PI are 54.5% and 73.7%, respectively, versus 25% and 60% of the MCA.¹³⁹ In contrast to chronic hypoxia, acute hypoxia (oxytocin challenge test at term) affects both the MCA and ACA.¹⁴⁰

Fetal brain sparing has been associated with behavioral problems in infancy, and fetuses with brain circulatory redistribution to the anterior cerebral artery (high umbilical/anterior cerebral artery ratio) have a higher risk of behavioral problems and other neurologic difficulties at the age of 18 months.¹⁴¹

Anatomy of the Ductus Venosus

The DV is a small-diameter vessel (0.5 mm in midgestation, not exceeding 2 mm at term)¹⁴² connecting the intraabdominal portion of the umbilical vein with the IVC, close to its entrance into the right atrium. The DV is localized in the liver, approximately between the right and left lobes. Figures 12-6 and 12-18 display the anatomy of the DV in relation with other vessels and structures in the liver.

Physiology of the Ductus Venosus

Approximately 20% to 50% of the umbilical venous blood, which has the highest oxygen saturation in the entire fetal circulation,¹⁴³ is shunted through the DV directly into the IVC. The rest of the blood within the umbilical vein goes to the portal vein.

Blood shunted through the DV into the IVC preferentially streams in the left compartment of this vessel, enters the right atrium, and crosses the foramen ovale to enter the left atrium and ventricle. This preferential streaming (via sinistra) ensures the supply of highly oxygenated blood to perfuse the heart (coronary circulation) and the brain, through the ascending aorta. In contrast, the blood contained in the IVC streams preferentially into the right compartment of the IVC and enters the right atrium and ventricle, the pulmonary artery, and the ductus arteriosus (via destra) (Figure 12-19).

The preferential streaming of oxygenated blood from the DV through the IVC and foramen ovale is possible by 2 mechanisms: (1) the high kinetic energy acquired by blood during its transit within the DV (because of the umbilico-caval pressure gradient and the smaller diameter of the DV than the umbilical vein), and (2) the anatomy of the right atrium inlet, with the foramen ovale orifice oriented towards the entrance of the IVC and the strategic insertion of the valve of the IVC, which is called the eustachian valve.

Shunting

The fraction of umbilical vein blood shunted through the DV into the IVC varies with gestational age, and it ranges between 20% and 50%.^144,145 It is close to 30% at midgestation, reaching a minimum of 18% at 18 to 20 weeks.¹⁴⁵ This indicates that most of the umbilical blood perfuses the fetal liver before entering the IVC and the systemic circulation. However, oxygen extraction in the liver is modest (10% to 15% reduction in oxygen saturation). Experimental evidence indicates that hypoxemia causes distension of the DV.¹⁴⁶ Therefore, fetuses with severe intrauterine growth restriction have significantly more shunting than those of appropriate weight for gestational age.^144,145,147

Sampling Techniques

Doppler interrogation of the DV can be achieved either in a midsagittal longitudinal plane of the fetal trunk (see Figure 12-6) or in an oblique transverse plane, through the upper fetal abdomen (Figure 12-20). In the midsagittal plane, the DV can be visualized as the continuation of the umbilical vein toward the vena cava. Advantages of sampling the DV in the midsagittal view are that color Doppler can be used to identify the vessel and that the angle of insonation is small. Alternatively, an oblique transverse view of the fetal abdomen can be obtained in the plane of the abdominal perimeter.

Visualization of the DV can be enhanced by color Doppler because the blood velocities within this vessel are high, and therefore aliasing can assist in the identification of the vessel (see Figures 12-6 and 12-20).

The sample volume should be placed at the origin of the DV from the umbilical vein. This is where color Doppler demonstrates the highest blood velocity. The angle of insonation should be as low as possible and always less than or equal to 30 degrees. High-quality Doppler interrogation needs to be conducted when the fetus is quiet and without fetal breathing movements. Because of the small diameter of the DV, we often ask mothers to hold their breath while sampling. This prevents the Doppler sample volume from falling outside the region of interest.

Morphology of the Ductus Venosus Waveform and Changes with Gestational Age

The DV waveform normally has forward flow throughout the entire cardiac cycle and a characteristic triphasic pulsatile pattern (Figure 12-21). Three waves, conventionally labeled as “S,” “D,” and “a” waves, are recorded during systole, early diastole, and atrial contraction (late diastole), respectively. The S wave has the highest velocity, followed by the D wave. The a wave has the lowest peak velocity.

Velocities in the DV are significantly higher than those recorded in the IVC. In the first trimester (11 to 12 weeks), velocities reach 20 to 30 cm/s (see Figure 12-21A). The mean peak velocity increases from 65 cm/s in the second trimester to up to 75 cm/s at term (see Figures 12-21B and C).¹⁴⁸ This increase in ductal venous flow velocities with gestational age has been attributed to an increased cardiac compliance.

In contrast to the peak velocities, there is a decrease in the peak velocity index for veins (PVIV) and in the pulsatility index for veins (PIV) with advancing gestational age. This is consistent with a decrease in cardiac afterload, which is, in turn, the consequence of reduced placental resistance and maturation in diastolic ventricular function.

Doppler Indices

Parameters used to describe the waveform of the DV include S or peak forward velocity recorded during ventricular systole, which is the highest velocity recorded; D, which is the peak forward velocity during early diastole (passive ventricular filling); and a, which is the lowest forward velocity during atrial contraction (late diastole). Table 12-5 describes the Doppler indices used by investigators. Cross-sectional^149-151 and longitudinal¹⁵² (Figures 12-22 and 12-23, and Table 12-6) reference ranges for these indices are available.

Moreover, DeVore et al have described a DV preload index, an angle-independent measurement that allows the estimation of the right ventricular preload in the second trimester (ventricular systole – atrial systole)/ventricular systole = (S – a)/S).¹⁵³

Clinical Correlations of an Abnormal Ductus Venosus Doppler Velocimetry

Abnormalities in the flow velocity waveform of the DV can be detected in intrauterine growth restricted (IUGR) fetuses with abnormal umbilical artery Doppler velocimetry, as well as in fetuses with structural heart disease, in which there is high pressure in the right atrium (tricuspid stenosis, Ebstein anomaly, etc).^154-157

The common denominator of these conditions is an increased volume/pressure in the right atrium, which has consequences on the venous drainage to the right heart. In such cases, the pressure oscillations in the right atrium will be transmitted to the central veins (ie, IVC) and to the DV, which will acquire a more pulsatile pattern.

The abnormalities in the DV include (1) increased PIV, (2) absence of end-diastolic flow, and (3) reverse end-diastolic flow (reverse a wave) (Figure 12-24).^{153,156,158-160}

The development of abnormalities in the DV Doppler velocimetry in IUGR fetuses is attributed to progressive impaired cardiac function, which characterizes the advanced stages of this condition.^160-165 Abnormalities in the DV Doppler velocimetry in IUGR fetuses are considered a major risk factor for stillbirth,⁹¹ fetal acidemia,^165-167 hypercapnia,¹⁶⁵ perinatal mortality,¹⁶⁸ and neonatal death.⁹¹ The performance of Doppler indices in the DV in the prediction of perinatal death is greater than that of abnormalities in the umbilical artery or evidence of brain sparing in the MCA.¹⁶⁸ Thus, reversal of flow in the DV is a major risk factor for impending fetal death and the development of an abnormal fetal heart rate tracing, which is frequently an indication for delivery.

Anatomy of the Inferior Vena Cava

The IVC drains blood from the lower extremities and the splanchnic territories into the right atrium. The 2 iliac veins join in the pelvis to form the lower part of the IVC, which travels upward in the retroperitoneal space, on the right side of the spinal column. Just before its entrance into the right atrium, the IVC enters a funnel-like structure, which also contains the orifices of the ductus venosus and the hepatic veins. This structure is called the “venous vestibulum” (see Figure 12-18).²³⁹

At the entrance into the right atrium, the eustachian valve (also known as the valve of the IVC) directs oxygenated blood from the ductus venosus and the hepatic veins into the left atrium. The eustachian valve is important during fetal life because it allows oxygenated blood to be shunted from the right to the left atrium and in this way maintains adequate oxygenation of the heart (via the coronary arteries) and brain (via the brachiocephalic arteries emerging from the aortic arch). After birth, this valve becomes a rudimentary structure.

Sampling Techniques

Doppler interrogation of the IVC is optimally performed in a sagittal section of the fetus. Color Doppler will aid in visualizing the IVC traveling close to the fetal spine, parallel and to the right of the descending aorta. The standard practice is to sample the IVC close to its entrance into the right atrium (2 to 4 mm; Figure 12-25).^{167,170,197,205} The distance of the sampling site from the right atrium affects the flow velocity waveform recordings as observed in Figure 12-26. However, some experts recommend sampling the IVC more distally from the venous entrance into the right atrium to avoid interference from the signals of the ductus venosus and the hepatic veins waveforms, which join the IVC in the venous vestibulum close to the right atrium.¹⁷¹ Rizzo et al reported that the highest reproducibility of the Doppler waveform of the IVC could be achieved by placing the sample gate between the entrance of the renal vein and the ductus venosus.¹⁷² The angle of insonation should be as close to 0 degrees as possible. Recording should be performed during fetal apnea and when there is no fetal movement. During fetal breathing, there is a gestational age-independent increase of the peak and time-averaged velocities.¹⁷³ The success rate in obtaining good-quality flow velocity waveforms of the IVC is about 89%.¹⁷¹

Indices

Reference ranges for the Doppler indices of the IVC are available (Figures 12-27 to 12-29).¹⁷⁴

Morphology of the Inferior Vena Cava Waveform and Changes with Gestational Age