Evaluation of a fetus for structural or functional cardiovascular disease has become routine now that there is widespread use of fetal ultrasound in obstetrical practice. In addition, greater understanding of the genetic basis for congenital cardiovascular defects has prompted screening of patients who might not have been referred for evaluation in the past. It is important to understand the uses and limitations of fetal echocardiography to optimally utilize this technology and to provide appropriate counseling to parents. This chapter provides a limited overview of fetal cardiology as a foundation for understanding selected aspects of fetal cardiovascular disease. Comprehensive references on fetal cardiology and, in particular, fetal echocardiography are listed at the end of this chapter.

Fetal echocardiography is the primary method for diagnosing fetal cardiovascular disease and monitoring progression and management of the disease process. In centers with experienced fetal echocardiography programs, significant congenital cardiovascular defects can be accurately diagnosed in approximately 95% of cases. Additional information about the application of echocardiography to assess cardiac and vascular function in the fetus is presented in Chapter 3.

A complete fetal echocardiogram is similar in scope to a postnatal transthoracic echocardiogram. Cardiac and great vessel anatomy and relationships, cardiac function, blood flow patterns, and cardiac rhythm are all assessed. A wide range of cardiovascular diseases can be detected and defined in the fetus, including simple and complex cardiovascular structural malformations, cardiomyopathies, tumors, and arrhythmias. Newer techniques of three- and four-dimensional echocardiography are being applied in many centers, but at present, the role of these modalities in improving detection, management, and follow-up requires additional research.

If indicated (see below), the first fetal echocardiogram is generally performed around 18 to 22 weeks’ gestation using a standard transabdominal approach. In some centers, transvaginal fetal echocardiography is offered as early as 11 weeks’ gestation. However, controversy exists regarding the usefulness of early transvaginal ultrasound, and it is not widely used at present. Initial transabdominal studies typically provide excellent resolution of the cardiovascular structures and are sufficiently early in gestation to allow for comprehensive planning.

Indications

As discussed in Chapter 15, the incidence of congenital cardiovascular malformations in the United States is around 10 per 1000 live births. The incidence of structural cardiovascular malformations in all pregnancies is not known but it is certainly higher because severe structural or functional cardiovascular malformations may be lethal in the fetus and some mothers elect to terminate the pregnancy if an extracardiac malformation or chromosomal abnormality is detected. In these situations, the presence of a congenital cardiovascular malformation may go unrecognized.

Because a complete diagnostic fetal echocardiogram is time consuming and labor intensive, fetal echocardiography is not well suited for routine screening of all pregnant women. Therefore, it is important to develop a strategy for appropriate targeted referrals for fetal echocardiography. The indications for fetal cardiac evaluation have been outlined in an American Heart Association Scientific Statement in 2014 (see Suggested Readings). These indications are based primarily on maternal, familial, or fetal factors. They are categorized and listed in Table 4-1.

Maternal Factors

Congenital cardiovascular disease in the mother increases the risk of a structural cardiovascular malformation in the fetus. However, the incremental increase in risk varies depending on the type of maternal cardiovascular disease. For example, a mother with an atrioventricular septal defect has a 10% to 12% risk of having a fetus with some type of congenital cardiovascular malformation. In contrast, a mother with tetralogy of Fallot (not associated with a microdeletion of chromosome 22q11) has only about a 2% risk of having an infant with cardiovascular disease. Given the autosomal dominant pattern of inheritance of some forms of long QT syndrome (LQTS), a mother with confirmed LQTS will have a 50% chance of the fetus having LQTS. Despite considerable progress, the complex genetics and inheritance of congenital cardiovascular malformations remain incompletely understood (see also Chapter 15). In the past, the situation was even more unclear because many children with congenital cardiovascular disease did not survive to reproductive age and fetal echocardiography was not available. As more women with congenital cardiovascular malformations survive into adulthood and have children, the relationship between maternal congenital cardiovascular disease and the risk to offspring will become clearer.

In addition to congenital cardiovascular disease in the mother, other maternal factors, including viral infections, certain medical conditions, and diabetes mellitus, may predispose the fetus to be at risk for congenital cardiovascular disease (see Chapter 15). The presence of a connective tissue disorder in the mother is associated with fetal atrioventricular block and cardiomyopathy. Specific maternal antibodies, namely, anti-SSA/Ro and anti-SSB/La, have been implicated in the development of fetal atrioventricular block and cardiomyopathy, but the precise cellular and molecular mechanisms are not entirely clear. Maternal connective tissue disease should prompt an evaluation for autoantibodies and fetal monitoring for the presence or development of atrioventricular block and cardiomyopathy. The corollary is that if an infant is born with congenital complete atrioventricular block, the mother should be evaluated for the presence of subclinical connective tissue disease. Over half of previously asymptomatic mothers are found to have laboratory evidence of connective tissue disease or later present with clinical findings. The most common disease found is Sjögren syndrome, followed by systemic lupus erythematosus.

Maternal anxiety and advanced maternal age are relative indications for fetal echocardiography. A normal fetal echocardiogram may be reassuring to a mother who, for whatever reason, is overly concerned about the possible presence of fetal cardiovascular disease. The value of fetal echocardiography in the setting of advanced maternal age (especially if amniocentesis is refused) has not been proven.

Familial Factors

The risk of recurrence of congenital cardiovascular malformations in subsequent siblings is related to the genetic basis of the particular defect or to other underlying maternal factors (see above). In general, the risk of recurrence is approximately two to five times greater than in the unaffected population. However, this figure may be much higher if there is underlying maternal disease that has already affected a previous fetus or if a known autosomal-dominant single-gene defect is present. In most cases of recurrent congenital cardiovascular malformations, the same defect recurs. However, even in the case of families with confirmed single-gene defects, the penetrance and phenotypic expression may be quite variable (Chapter 15). The presence of other forms of birth defects in previous children is also associated with a higher incidence of cardiovascular malformations.

Fetal Factors

Obstetrical ultrasound evaluation is routine and common. However, a routine obstetrical ultrasound evaluation does not constitute a complete fetal echocardiogram. A normal four-chamber screen (Figure 4-1) is essential for excluding many serious major structural congenital heart defects, but a number of malformations may be missed (see “Limitations of Fetal Echocardiography” below). It is estimated that the four-chamber view is abnormal in about 1 in 500 pregnancies and in about 60% of fetuses with major structural cardiovascular malformations. The value of a routine obstetrical ultrasound as a screen for fetal cardiovascular malformations is improved when a sweep to evaluate the right and left ventricular outflow tracts is included with the four-chamber screen. More recently, the so-called three-vessel-with-trachea view, which images the main pulmonary artery trunk, ascending aorta, and superior vena cava to assess for conotruncal abnormalities, is recommended. Detection of cardiovascular disease increases to 90% if all three views are recorded.

An abnormal four-chamber view or outflow tract screen should prompt referral for a complete fetal echocardiogram. In addition, detection of specific cardiovascular malformations or extracardiac malformations constitutes an indication for a complete fetal echocardiogram. Extracardiac anomalies that have a high association with cardiovascular malformations include omphalocele, diaphragmatic hernia, duodenal atresia, tracheo-esophageal fistula, cystic hygroma, and single umbilical artery. Many chromosomal abnormalities (eg, trisomy 21) are associated with congenital cardiovascular malformations. If the karyotype analysis from amniocentesis is abnormal, fetal echocardiography should be performed. Finally, nuchal translucency is being used with increasing frequency as a screen for congenital cardiovascular disease. By itself, increased nuchal translucency is of only moderate specificity, but when associated with tricuspid insufficiency or an abnormal flow pattern in the ductus venosus, the likelihood of congenital cardiovascular disease is high. In addition, the greater the nuchal translucency is, the more likely congenital cardiovascular disease is present. Currently, many perinatologists use a nuchal translucency greater than the 95th percentile as an indication for fetal echocardiography.

Twin pregnancies are characterized by an increased incidence of fetal complications, especially in monozygotic twins. Most monochorionic twins share blood supply through vascular anastomoses in the placenta. In 10% to 20% of monozygous twin pregnancies, this shared blood supply is unequal and results in twin-to-twin transfusion syndrome. Severe twin-to-twin transfusion syndrome produces asymmetrical fetal growth and, if untreated, results in death of one or both fetuses in over 80% of cases, especially if this condition is noted before 28 weeks’ gestation. Cardiovascular compromise is common in the recipient twin. Fetal echocardiographic findings include ventricular hypertrophy and dilation, tricuspid regurgitation, and, less commonly, mitral regurgitation. The prevalence of pulmonary valve stenosis is fourfold greater in twin-to-twin transfusion syndrome than in twin pregnancies without evidence of twin-to-twin transfusion syndrome. It has been proposed that progressive right ventricular hypertrophy and severe tricuspid regurgitation result in decreased flow across the pulmonary valve with resulting acquired pulmonary stenosis (or atresia in severe cases). A variety of treatments have been used for twin-to-twin transfusion syndrome, including selective fetocide, serial amnioreduction, septostomy of the intertwin membrane, and endoscopic laser photocoagulation. Selective endoscopic laser photocoagulation of anastomotic vessels is currently the primary treatment in many centers and should be considered when twin-to-twin transfusion syndrome is diagnosed, regardless of the initial severity.

Hydrops fetalis is a serious fetal condition defined as abnormal fluid accumulation in two or more fetal compartments. Fluid may collect in the pleural, pericardial, and/or abdominal cavities. Excess fluid often collects in the skin as well. In some cases, there is placental edema and/or polyhydramnios. Fetal ultrasound is invaluable in diagnosing, assessing severity, and monitoring treatment of hydrops fetalis. Hydrops fetalis has many causes (Table 4-2), most of which are not related to primary cardiovascular abnormalities. The most common cause of hydrops fetalis is severe anemia, which can be due to a variety of conditions. In the past, if the fetus was not anemic, the etiology of hydrops fetalis was often undefined (idiopathic), but more recently, the list of conditions that can cause hydrops has expanded. With greater accuracy in diagnosis, it has become clear that a number of genetic abnormalities and inborn errors of metabolism (especially lysosomal storage diseases) can cause hydrops fetalis. A cause is now identified in approximately 75% cases of nonimmune hydrops fetalis.