Congenital heart disease comprises the most common form of congenital anomaly found in humans, affecting 8 of every 1000 live births and 10 to 12 out of every 1000 pregnancies. Over the past 20 years, fetal echocardiography has emerged as a reliable and accurate means to diagnose these problems associated with cardiac structure and function prior to birth. As imaging technologies continue to improve, a higher percentage of congenital heart defects and abnormalities of fetal cardiovascular function can be detected prior to birth, allowing practitioners to counsel parents about their unborn child’s expected outcome and to implement prenatal and perinatal management strategies in order to maximize postnatal outcome.

In contrast to postnatal circulation, in which the pulmonary and systemic circulation are arranged in series, the fetal circulation is arranged in parallel because the placenta, rather than the lungs, serves as the site of oxygenation and ventilation. As a consequence, the right ventricle pumps approximately 55% to 60% of the combined cardiac output, whereas the left ventricle pumps approximately 40% to 45%.1 As shown in Figure 3-1, the fetal blood flow patterns are optimized to deliver oxygen and nutrition to vital organs, while shunting blood away from less important structures. Indeed, the placenta has extremely low resistance in order to promote blood flow to this site. Within the capillary bed of the placenta, oxygen is exchanged for carbon dioxide. A single umbilical vein then leaves the placenta carrying richly oxygenated blood back to the fetus through the umbilical cord. To bypass most of the liver, the umbilical vein inserts into the ductus venosus, which then connects with the inferior vena cava to enter the right atrium. The angle at which the ductus venosus inserts into the inferior vena cava–right atrium junction directs most of the richly oxygenated blood across the foramen ovale and into the left atrium and left ventricle. The left ventricle, in turn, perfuses the coronary arteries and the cerebral vasculature. These fetal physiologic adaptations ensure that the most richly oxygenated blood is delivered to the most vital structures in need of oxygen, namely the myocardial and cerebral circulations. Similarly, the most deoxygenated blood returning from the superior vena cava is directed to the tricuspid valve and into the right ventricle, which pumps blood into the main pulmonary artery and across the ductus arteriosus to return to the descending aorta and ultimately to the umbilical arteries. Because the fetal lungs are compressed and not responsible for oxygenation and ventilation prior to birth, the resistance within the pulmonary vasculature is quite high to ensure that deoxygenated blood crosses the ductus arteriosus rather than entering the fetal lungs, to return deoxygenated blood to the site of oxygenation within the fetus, namely the placenta.

Compared to the adult myocardium, the fetal myocardium demonstrates unique myocardial properties. Fetuses have impaired myocardial relaxation, secondary to a greater percentage of noncontractile elements2 and less efficient removal of calcium from troponin C within the cardiac myocyte.3 As a result, ventricular filling in the fetus is accomplished predominantly by active atrial contraction rather than passive ventricular filling. Inherent stiffness of the fetal myocardium underlies the mechanism for fetal hydrops. Any disease process that results in a slight increase in atrial pressure is poorly tolerated, leading to the findings of hydrops fetalis, characterized by fluid in any two extravascular spaces, such as ascites, peripheral or scalp edema, pleural effusions, or pericardial effusions.

Screening fetal echocardiograms are typically performed between 18 and 22 weeks of gestation. At these gestational ages, there is adequate amniotic fluid volume to allow good visualization of the cardiac structures and vasculature for an accurate diagnosis. After 30 weeks of gestation, the increase in fetal body mass and the shadowing effects of the fetal ribs may make image acquisition more difficult. However, early transabdominal and transvaginal fetal echocardiography may be performed as early as 11 to 14 weeks of gestation in high-risk pregnancies, such as those with aneuploidy, those with increased nuchal translucency during scanning at 10 to 14 weeks, and those with a family history of congenital heart disease.4

Current indications for fetal echocardiography, as recommended by the American Society of Fetal Echocardiography, are outlined in Table 3-1.5 These indications are broken down into maternal and fetal indications. Twenty years ago, the most common indications for fetal echocardiography were family history of congenital heart disease, a 2-vessel cord, maternal diabetes mellitus, or maternal exposure to teratogens. However, less than 10% of these referrals actually had congenital heart defects. In contrast, as imaging technologies have continued to improve, the most common indication for referral today is an abnormal obstetrical ultrasound evaluation, yielding congenital heart defects and abnormalities of fetal cardiovascular function in approximately half of these referrals.6 Novel, emerging indications for fetal echocardiography include a nuchal translucency measuring greater than 3 mm between 10 and 14 weeks of gestation7 and in vitro fertilization, particularly if the procedure includes intracytoplasmic sperm injection.8 Table 3-2 summarizes maternal medical conditions and medication exposures with associated congenital heart lesions.

Cross-sectional imaging remains the gold standard for the diagnosis of structural cardiac disease during fetal life. The Pediatric Council of the American Society of Echocardiography recommends obtaining multiple cross-sectional tomographic views of the heart in order to make an accurate diagnosis.5 Curvilinear ultrasound transducers, using ultrasound frequencies between 3 and 7 MHz, allow for better image acquisition on the gravid uterus. Fetal echocardiography should include an apical 4-chamber view of the heart, an apical 5-chamber view, a long axis view of the left ventricular outflow tract, a right ventricular outflow tract view, a short axis view at the outflow tracts, a short axis view at the level of the ventricles, a long axis view of the superior and inferior vena cavae, a view of the ductal arch, and a view of the aortic arch5 (Figure 3-2). The fetal heart rate should be documented, and any arrhythmia confirmed with M-mode imaging. The diameters of all valves should be measured in systole at right angles to the plane of flow.5 Reference ranges for the diameters of all valves over the course of gestation have been published.9 Cardiac dysfunction may be assessed by cross-sectional interrogation by the presence of ascites, pleural or pericardial effusions, skin edema, and cardiomegaly, as defined by a ratio of cardiothoracic areas of greater than 0.36.10 A cardiothoracic area ratio greater than 0.6 is associated with an extremely poor outcome.11

Color Doppler interrogation adds to the assessment of fetal cardiovascular well-being by establishing the degree of valvular stenosis and regurgitation, if present. Mild tricuspid regurgitation may be seen throughout gestation and is frequently a benign finding,12,13 but tricuspid regurgitation detected during early scanning, from 11 to 14 weeks, may be a marker for aneuploidy, even in the absence of structural heart disease.14 In contrast, regurgitation across the mitral, pulmonic, or aortic valves is usually not a normal finding and suggests pathology, secondary to underlying structural cardiac disease or fetal cardiac failure. Cardiovascular physiology can also be assessed by color Doppler echocardiography by determining the direction of blood flow. In the normal fetal circulation, the direction of shunting is right to left at both the patent foramen ovale and the ductus arteriosus. Abnormal directions of flow at these sites may suggest cardiac disease. For example, left-to-right flow at the patent foramen ovale or bidirectional shunting through the ductus arteriosus with reversal of flow in the transverse arch may indicate inadequacy of the left ventricle.15,16

Doppler echocardiography adds tremendous value to the assessment of the fetal cardiovascular system. Expected Doppler flow patterns for the umbilical artery, umbilical vein, middle cerebral artery, ductus venosus, atrioventricular valve inflow, and ductus arteriosus have been well described in the literature at each gestational age. In fetuses with altered hemodynamics secondary to congenital heart disease, intrauterine growth retardation, twin to twin transfusion syndrome, or significant extracardiac anomalies known to impact the fetal cardiovascular system, Doppler echocardiography may help to quantify the degree of cardiac compromise that otherwise may not be evident with 2-dimensional and color Doppler techniques alone.

Umbilical Artery and Vein

The umbilical cord, usually containing 2 arteries and 1 vein, is a vital structure linking the fetus to the placenta. The presence of a single umbilical artery may be an isolated finding or may be associated with growth retardation or chromosomal abnormalities, particularly when there are multiple congenital anomalies detected on fetal ultrasonography.17 Pulsed wave Doppler interrogation of the umbilical cord is best performed parallel to flow within the midportion of the cord during fetal apnea. Doppler sampling within the umbilical artery reflects downstream resistance within the placenta. As discussed earlier, the resistance within the umbilical artery is generally quite low in order to promote blood flow to the placenta so that nutrients and gases may be effectively exchanged. As shown in the top left-hand panel of Figure 3-3, the Doppler flow pattern within the umbilical artery is characterized by continuous forward flow both in systole and in diastole. In cases of intrauterine growth retardation, the diastolic velocity within the umbilical cord decreases and may even be absent—see top right-hand panel of Figure 3-3. Fetuses with diastolic flow reversal within the umbilical artery, as shown in the bottom left-hand panel of Figure 3-3, are at risk for an in utero demise.

Conversely, Doppler assessment of the umbilical vein reflects central venous pressure. As central venous pressure rises on account of heart failure, complete atrioventricular block, or severe tricuspid regurgitation, changes within the Doppler flow patterns are first seen in the inferior vena cava, then in the ductus venosus, and finally in the umbilical vein. The umbilical venous Doppler flow pattern is usually described as phasic, low-velocity flow—see the top left-hand panel of Figure 3-3. Respiratory variation may be seen if the Doppler sample is not acquired during fetal apnea. With increases in central venous pressure, notching is first seen at end-diastole. In cases of severe compromise, venous pulsations—consisting of s, d, and a waves, may be seen—as shown in the bottom right-hand panel of Figure 3-3.

Ductus Venosus

The ductus venosus is a key structure in fetal life that enables most of the highly oxygenated blood returning from the umbilical vein to enter the inferior vena cava, thereby bypassing the liver. Absence of the ductus venosus is associated with an increased incidence of fetal anomalies, including congenital heart disease, chromosomal anomalies, and fetal hydrops—especially in cases where the liver is bypassed entirely and all umbilical venous return is directed into the right atrium. Given its proximity to the heart, abnormalities in the ductus venosus Doppler flow pattern may be seen prior to any changes within the umbilical vein. The ductus venosus Doppler flow pattern is compromised of s, d, and a waves (Figure 3-4). After 14 weeks of gestation, flow within the ductus venosus should be all antegrade with no reversal with atrial contraction. Over the course of gestation, resistance within the ductus venosus in normal fetuses progressively declines. In fetuses with hemodynamic abnormalities associated with elevated central venous pressure, the a -wave velocity, corresponding to atrial contraction, decreases initially and then becomes reversed as shown in Figure 3-4. Pathologic conditions associated with a -wave reversal in the ductus venosus include complete atrioventricular block and severe tricuspid regurgitation, as seen in Ebstein anomaly and in the recipient twins of the twin–twin transfusion syndrome.

Middle Cerebral Artery

Doppler assessment of the middle cerebral artery provides vital information about overall fetal health as well as about the cerebrovascular resistance. Figure 3-5 demonstrates the normal Doppler flow pattern of the middle cerebral artery. Generally, most of the flow occurs during systole with only a small amount of flow in diastole. The peak systolic velocity within the middle cerebral artery increases over the course of gestation, although an elevated peak systolic velocity within the middle cerebral artery may suggest an underlying diagnosis of fetal anemia. In fetuses with normal hemodynamics, the resistance within the cerebral vasculature is greater than the placental resistance. However, in fetuses with chronic hypoxia or inadequate cardiac output, there may be “cephalization” of flow characterized by a ratio of resistance in the middle cerebral artery compared to the umbilical artery of less than 1, otherwise known as the “brain-sparing effect.”

Altered flow patterns within the fetal brain have also been well described in fetuses with congenital heart disease. Compared to normal fetuses, fetuses with left-sided obstructive lesions, such as hypoplastic left heart syndrome, have decreased resistance within the middle cerebral artery, likely as a mechanism to improve flow to the fetal brain.18 Whether this abnormal flow pattern impacts fetal brain development is an ongoing area of investigation, although abnormalities of the brain have been described in neonates with congenital heart disease even prior to any surgical palliation.19-21 Conversely, in fetuses with increased blood flow to the fetal brain secondary to right-sided obstructive lesions, the cerebrovasculature vasoconstricts in an attempt to limit cerebral blood flow.18 As a consequence, the resistance within the middle cerebral artery is increased in these fetuses compared to normal fetuses.

Tricuspid and Mitral Inflow

As previously discussed, the fetal myocardium is comprised of greater noncontractile elements compared to the mature myocardium.2 As a consequence of this inherent diastolic dysfunction, there is decreased passive ventricular filling and a greater percentage of ventricular filling during atrial contraction. This, in part, explains why fetuses with complete heart block may develop hydrops fetalis. Without the contribution of atrial contraction to ventricular filling, preload may become compromised, resulting in an overall decreased cardiac output.

Figure 3-6 demonstrates the normal biphasic inflow pattern in the fetus. As shown below, there is a lower E-wave velocity, representing passive ventricular filling, and a dominant a-wave velocity, representing active atrial contraction. The ratio of the E wave to the a wave increases over the course of gestation as the relaxation properties of the fetal myocardium improve. With altered ventricular compliance secondary to ventricular hypertrophy, as seen in the recipient twin of the twin–twin transfusion syndrome, or endocardial fibroelastosis, as seen in critical aortic stenosis and evolving hypoplastic left heart syndrome, the normal biphasic inflow pattern may fuse into a single peak inflow, as shown in Figure 3-6.

Ductus Arteriosus

The ductus arteriosus enables the oxygen-poor blood pumped by the right ventricle to bypass the fetal lungs and return to the placenta via the descending aorta. The Doppler flow pattern, as shown in Figure 3-7, is laminar with predominantly systolic flow and a smaller amount of diastolic flow. The ductus arteriosus should be large and unrestrictive to avoid passage through the fetal lungs, which are under high resistance during fetal life. Indeed, significant constriction of the ductus arteriosus, as shown in Figure 3-7, imposes greater afterload on the right ventricle, which can lead to right ventricular hypertrophy, tricuspid regurgitation, and ultimately, right ventricular failure and intrauterine fetal demise. Numerous medications, most notably corticosteroids, high-dose aspirin, and prostaglandin synthetase inhibitors, have been implicated as causing ductal constriction. Figure 3-7 shows the Doppler flow pattern of the ductus arteriosus in a fetus with severe ductal constriction. Closure of the ductus arteriosus in utero with evidence for right ventricular failure should prompt clinicians to strongly consider delivery of the baby to prevent an in utero fetal demise.