Optimal imaging technique for Doppler interrogation of the ductus venosus has been well described [12, 13]. The ultrasound modalities include two-dimensional, color flow Doppler, and spectral Doppler imaging. The essential guidelines are as follows.

The high-pass filter is set as low as permitted by the device and is usually set at about 50 Hz level. An adequate Doppler frequency range should be selected to accommodate peak velocities without aliasing. The acoustic power output (the mechanical and thermal indices) should be set at a level as low as practically achievable for adequate image quality following the ALARA principle [14]. Anterior sagittal fetal plane is optimal for imaging the ductus (Fig. 12.2). However, posterior sagittal plane may also be helpful. These approaches allow viewing the ductus venosus in a long axis, displaying aliased high velocity color flow at the isthmus and enabling optimal pulsed spectral Doppler interrogation with a minimal insonation angle. In difficult fetal positions, an oblique cross sectional view may be the only choice; however, this will limit imaging at an optimal angle. In early pregnancy, the fetal image should be large enough to include just abdomen and thorax. This minimizes measurement errors related to small size. The sample volume should be adjusted to include only the target vein in order to avoid collecting signals from other veins in proximity, such as the umbilical vein, the hepatic vein or the inferior vena cava. Imaging should be performed only when the fetus is at rest, without body movements, breathing or hiccups.

In normal pregnancies, blood flow in the ductus venosus is directed toward the fetal heart. The Doppler waveform is triphasic with two peaks and a trough reflecting the phases of the fetal cardiac cycle (see Fig. 12.2). The first peak is the highest velocity during the ventricular systole and is designated as the S wave. The second peak, termed the D wave, is the highest velocity during the ventricular diastole and is lower than the S wave. The trough, called the a-wave, is the lowest velocity of the Doppler waveform corresponding to the minimum velocity during the atrial contraction. The Doppler waveforms from the ductus venosus can be analyzed in terms of the actual velocity values, which require an optimal insonation angle and angle correction. Alternatively, various indices of pulsatility have been described which obviates the need for angle correction. In all these measurements the maximum frequency shift envelope of the waveform is utilized (see Fig. 12.2).

In clinical practice, the most relevant and frequently used attribute is the a-wave, which is related to the atrial contraction. A zero or negative waveform indicates an increased end-diastolic filling pressure in the right heart (Fig. 12.3).

In early pregnancy, the velocity of blood flow in the ductus venosus increases with gestational age. The increase is throughout the fetal cardiac cycle. In a cross-sectional study of 262 normal singleton fetuses between 8 and 20 weeks gestation, van Splunder and associates noted a significant nonlinear rise in S, D and time-averaged peak velocity (Vta) but a significant decline in the pulsatility index for veins (PIV) [15]. The Vta increased almost fourfold. Prefumo and colleagues measured the ductus venosus velocity parameters between 10 and 14 weeks in 201 normal fetuses in a cross-sectional study [16]. During this period, the mean S wave increased from 27 to 33.6 cm/s, the mean a-wave from 5.9 to 7.8 cm/s, and the time-averaged peak velocity from 19.4 to 25.3 cm/s. These increases level off beyond the first half of pregnancy. The reference ranges for the ductus venosus Doppler velocity components from this study are depicted in Figs. 12.4, 12.5, 12.6, and 12.7.

Fetal breathing movements produce intrathoracic pressure fluctuations, leading to changes in the venous pressure dynamics. Breathing induced pressure gradients of up to 22 mmHg across the ductus venosus have been estimated in fetuses during 18–40 weeks of pregnancy utilizing the Bernoulli equation [17]. This is the rationale for not assessing the ductus venosus Doppler hemodynamics during fetal breathing. Breathing movements in early gestation are not regular and become more frequent as the fetus approaches mid-gestation [18]. There is a dearth of information regarding the quantitative effects of breathing movements on precordial venous dynamic in early pregnancy. Fetal movements will also affect the Doppler shift.

Fetal heart rate affects ductus venosus Doppler waveform. Bradycardia allows an increased venous return and atrial filling, leading to an enhanced atrial contraction and, consequently, an enhanced a-wave. In a sheep model, Gudmundsson and coworkers noted changes in ductus venosus velocity waveform directly related to fetal bradycardia consequent to fetal hypoxemia, [19]. Any increase in the fetal myocardial compliance will lead to changes in the ductal waveform. Thus, hypoxia, acidosis or intra-thoracic lesions such as pleural effusion pressing on the heart lower cardiac compliance, leading to augmented a-waves [9, 13]. Blood viscosity also modifies venous Doppler waveforms, which is seen in fetal anemia. Lam and co-investigators reported significant increases in S, a-wave and Vta in nonhydropic fetuses between 12 and 13 weeks with homozygous alpha thalassemia-1 [20]. This was attributed to lower blood viscosity in anemia and also to hypoxia.

The most frequent and important utilization of ductus venosus Doppler in the first trimester of pregnancy is for aneuploidy screening. Various investigators have demonstrated its efficacy, with or without the nuchal translucency and various biomarkers. Selected reports are discussed below and summarized in Table 12.1 [21–30].

Borrell and colleagues reported Doppler velocimetry of the ductus venosus, prior to performing invasive diagnostic procedures for trisomy 21, in 534 consecutive fetuses of 10–18 weeks of gestation [21]. Trisomy 21 was present in 11 fetuses, eight of whom had venous pulsatility index >95th centile, and three had the a-wave below 5th centile. Matias and coworkers performed Doppler velocimetry of the ductus venosus, just before fetal karyotyping, in 486 consecutive singleton pregnancies between 10 and 14 weeks [22]. Of the 63 fetuses with chromosomal anomaly, 57 (90.5 %) had reverse or absent a-wave. Abnormal ductus venosus Doppler was also observed, however, in 13 (3.1 %) of the 423 euploid fetuses. Multivariate regression analysis demonstrated that only the abnormal a-wave offered a significant independent discrimination between the euploid and the aneuploid cases.

In a cohort of about 20,000 singleton pregnancies, Maiz and colleagues performed a combined first-trimester screening test, comprising maternal age, fetal nuchal translucency thickness, fetal heart rate, serum free beta-human chorionic gonadotropin, pregnancy-associated plasma protein-A (PAPP-A), and the ductus venosus Doppler [29]. The a-wave was reversed in 66–75 % of aneuploid, but in only 3.2 % of euploid fetuses. Universal inclusion of the first-trimester ductus venosus Doppler would detect 96 %, 92 %, 100 % and 100 % of trisomies 21, 18 and 13 and Turner syndrome, respectively, at a false-positive rate of 3 %. Similar detection rates were achieved in a two-step strategy with a false-positive rate of 2.6 %, necessitating ductus venosus Doppler in only 15 % of the total population.

It should be appreciated that most fetuses with abnormal ductus venosus Doppler are euploid and not all fetus with aneuploidy will have abnormal findings. As shown in Table 12.1, which summarizes several studies on first-trimester ductus venosus Doppler, abnormal Doppler findings were present in 70 % of aneuploid fetuses, but only in 4 % of the euploid fetuses (see Table 12.1).

Obviously, prenatal noninvasive risk assessment for chromosomal abnormalities during early gestation involves multiple modalities, such as the sonographic assessment of nuchal translucency and measurement of multiple analytes. The efficacy of incorporating the ductus venosus Doppler in these algorithms is further discussed later.

Ductus venosus Doppler waveforms reflect fetal central hemodynamics, especially that of the right heart. Functional and anatomical abnormalities are expected to alter this waveform. This prompted many to explore its screening potential for the early detection of fetal cardiac disease.

Matias and coworkers performed Doppler velocimetry of the ductus venosus in 200 singleton fetuses with increased nuchal translucency, at 10–14 weeks’ gestation, immediately before fetal karyotyping [22]. The results suggested that in euploid fetuses with increased nuchal translucency, the presence of abnormal ductus venosus blood flow recognized those with major cardiac defects.

In a study involving over 41,000 euploid fetuses, reversal of ductus venosus a-wave was observed in about 28 % of the fetuses with cardiac anomalies and in about 2 % of the fetuses with no cardiac anomalies [31]. The authors estimated that comprehensive fetal echocardiography would detect approximately 39 % of major cardiac defects, at an overall false-positive rate of about 3 %, in cases with nuchal translucency above the 99th centile and those with reversed a-wave, independent of the nuchal translucency measurement.

This has been further confirmed, more recently, by Borrell and associates who studied the efficacy of various first-trimester ultrasound screening strategies for the recognition of major cardiac malformations, in euploid fetuses [32]. The sonographic methods included fetal nuchal translucency and Doppler indices of the ductus venosus. If the ultrasound findings were abnormal, early echocardiography was recommended. Verification of the fetal cardiac status was performed by fetal echocardiography in mid- and late gestation, neonatal assessment or autopsy. Of the 37 euploid fetuses with a major cardiac malformation, the nuchal translucency was above the 99th centile in 27 % cases and the ductus venosus a-wave was absent or reversed in 39 % of the fetuses. The authors noted a 47 % detection rate of major heart defects, with a false positive rate of about 3 %.

These and other investigations suggest a role for ductus venosus Doppler to identify early those fetuses at a higher risk of CHD. Early fetal echocardiography can be challenging and may not obviate the need for comprehensive ultrasound examination at mid-pregnancy. However, Zidere and associates recently demonstrated that, in expert hands, it could achieve a high degree of accuracy [33]. Future research should further address the effectiveness of early fetal echocardiography in clinical practice.

Over the recent years, there has been a progressively wider use of Doppler echocardiography for assessing fetal cardiac function in early pregnancy. Of the various aspects of fetal cardiac function, the tricuspid flow patterns have received the most attention, especially regarding its association with congenital cardiac malformations and aneuploidy.