The diagnosis of fetal arrhythmias has become increasingly common as echocardiographic evaluation of the fetal heart has improved and been pursued earlier in gestation. Two-dimensional echocardiography can distinguish normal from disordered cardiac anatomy as early as 16 weeks of gestation (Kleinman et al., 1980; Allan et al., 1983, 1984a). Similarly, fetal arrhythmias can be accurately characterized with the addition of M-mode echocardiography (Allan et al., 1983; Devore et al., 1983). Although the vast majority of fetal arrhythmias reported are either extrasystoles (75%) or tachyarrhythmias (15%), fetuses with bradyarrhythmia due to complete heart block (CHB) account for 9% of all cases (Kleinman and Evans, unpublished data, 1988). CHB is seen in association with severe congenital heart disease in up to 53% of cases (Schmidt et al., 1991). In this setting the prognosis is poor, with a survival rate of less than 15% (Shenker, 1979; Teteris et al., 1979; Allan et al., 1983; Crawford et al., 1985; Cameron et al., 1989). However, CHB complicates structural congenital heart disease in only 0.4% to 0.9% of the cases (Camm and Bexton, 1984; Olah and Gee, 1993). CHB is observed with normal cardiac anatomy in up to 50% of cases (Kleinman and Evans, unpublished data, 1988). CHB with normal cardiac anatomy is usually associated with transplacental passage of maternal antibodies, anti-SSA or anti-SSB (anti-Ro or anti-La), in mothers with connective-tissue diseases (McCue et al., 1977; Scott et al., 1983; Litsey et al., 1985; Taylor et al., 1988).

The most common form of congenital heart block seen in the fetus is third-degree, or complete, atrioventricular (AV) block. First-degree AV block is the prolongation of the P–R interval and is difficult to detect prenatally. Second-degree AV block occurs either as a progressive lengthening of the P–R interval, with resulting dropped beats (Wenckebach phenomenon), or as a fixed P–R interval with a ratio of transmission of atrial beats to ventricular beats of 2:1, 3:1, 4:1, etc. Third-degree AV block occurs when there is complete dissociation of atrial and ventricular rates with no transmission of atrial beats to the ventricles.

Antibodies to soluble ribonuclear proteins, anti-Ro (Sjögren syndrome antigen-A, SS-A) and anti-La (Sjögren syndrome antigen-B, SS-B) have been demonstrated in the serum of affected fetuses and their mothers (Franco et al., 1981; Kephart et al., 1981; Miyagowa et al., 1981). CHB in fetuses with structurally normal hearts is almost uniformly associated with the presence of anti-Ro or anti-La antibodies. Anti-Ro and anti-La antibodies have been demonstrated to bind to fetal heart conduction tissue (Deng et al., 1987; Harsfield et al., 1991). The pathophysiology of CHB involves the transplacental passage of maternal autoantibody, anti-Ro, which binds to an antigen in the fetal heart conduction system with consequent inflammation and fibrosis. The fetal and neonatal heart contains the body’s highest concentration of Ro antigen (Wolin and Steitz, 1984; Harley et al., 1985; Deng et al., 1987). IgG deposits have been demonstrated in the cardiac tissues of affected infants (Litsey et al., 1985; Lee et al., 1987). Studies in vitro, using anti-Ro and anti-La antibodies, have demonstrated that anti-Ro antibodies selectively bind to newborn myocardium but not to adult myocardium and that this binding inhibits repolarization (Alexander et al., 1992).

Although it is thought that anti-Ro and anti-La antibodies play an important role in the pathogenesis of fetal CHB, some authors have suggested that there must be a cofactor (Taylor et al., 1988). The mothers of infants with CHB almost always have anti-Ro and anti-La antibodies. Fetal CHB, however, develops in only 1% to 2% of anti-Ro/anti-La antibody positive mothers, and usually occurs between 20 and 24 weeks’ gestation. Since the majority of mothers with these antibodies have normal pregnancies, this implies that a second factor is necessary for the development of CHB. It has been suggested that viral infections may initiate immune damage by influencing antigenic expression. Ro and La ribonucleoproteins may become immunogenic by forming complexes with viral genomes (Venables et al., 1983). Interestingly, an increased frequency of antibodies to cytomegalovirus has been observed in mothers of babies with CHB (Peckham et al., 1983; Taylor et al., 1988).

In cases in which maternal anti-Ro/anti-La antibodies are not responsible for CHB, prolonged QT syndrome or viral infection may be responsible (Peckham et al., 1983).

The presence or absence of subendocardial fibroelastosis should be noted in cases of CHB. This is an echogenic appearance to the inner lining of the cardiac chambers, most often affecting the ventricles but also can affect the atria. This is thought to be due to subendocardial ischemia and is usually a sign of more severe myocardial injury, which without treatment is associated with a poor prognosis (Jaeggi et al., 2004).

CHB during fetal life is uncommon, with an incidence of approximately 1 in 20,000 to 1 in 25,000 livebirths (McHenry and Coyler, 1969; Michaelson and Engle, 1972; Gochberg, 1984). However, because many fetuses with CHB die in utero, the true incidence of fetal CHB is likely to be somewhat higher than this.

The most common reason for referral for evaluation for fetal CHB is the detection of a slow or irregular heart rate on routine obstetric examination (Schmidt et al., 1991). The median gestational age at referral for fetal CHB is 26 weeks, but may range from 17 to 38 weeks (Schmidt et al., 1991). More than half of fetuses with CHB will have associated structural heart disease, making assessment of fetal cardiac anatomy essential. The diagnosis of CHB can be confirmed sonographically by demonstrating atrial and ventricular rate discrepancies. If detected early, type 1 or 2 second-degree AV block may be observed. M-mode examination may be particularly useful to independently confirm atrial and ventricular rates (Crowley et al., 1983). It is also important to sonographically assess myocardial function, as immune complex deposition and fetal inflammatory reaction may result in myocarditis and significant myocardial dysfunction.

A complete fetal survey should be performed, with special attention paid to the presence or absence of hydrops, as indicated by pericardial or pleural effusions, ascites, or skin edema. Echocardiographic assessment should include measurement of ventricular escape rate and atrial rate. An atrial rate of less than 120 beats per minute (bpm) should raise the possibility of a missed structural heart defect. In addition, assessment of stroke volume, left and right ventricular ejection fraction, combined ventricular output, and the presence and severity (or absence) of AV valvular insufficiency should be noted (Takomiya et al., 1989; Veille et al., 1990). Valvular insufficiency can be diagnosed by Doppler echocardiography. Peak systolic flow velocities in the ascending aorta and diastolic umbilical flow velocities should be assessed as indirect indicators of cardiac output, and should be measured as a basis for comparison for serial echocardiographic assessment.

Doppler ultrasound assessment of the umbilical artery has been used to estimate impedance to flow in the placental circulation. However, because calculations depend on the time taken for the velocity of flow to decay in diastole, the prolonged diastolic component in CHB limits the value of this technique (Olah et al., 1991; Olah and Gee, 1993). Complete absence or reversal of flow during diastole in CHB, however, has the same clinical significance as in cases in which the heart rate is normal (Olah et al., 1991). This form of sonographic assessment is thought to be particularly useful in CHB because of its association with anti-Ro antibodies and antibodies in connective-tissue disease, such as systemic lupus erythematosus, in which placental infarction and immunoglobulin deposition are frequently encountered (Guzman et al., 1987; Veille et al., 1990). Increases in placental resistance may be sufficient to precipitate cardiac decompensation, even in the absence of further slowing in the ventricular escape rate.

Growth restriction may occur as a result of fetal CHB. Therefore, serial measurements of biparietal diameter, abdominal circumference, and long bones should be performed at bimonthly intervals to assess fetal growth.

Measurement of the cardiothoracic ratio should also be performed by two-dimensional echocardiography (Paladini et al., 1990). An increase in the cardiothoracic index beyond the normal range may assist in predicting the extent of lung compression and possible pulmonary hypoplasia, as well as the severity of cardiac failure as indicated by cardiac enlargement (Olah and Gee, 1993).

When evaluating a fetus with bradycardia, the differential diagnosis includes heart block as a complication of structural heart disease, heart block in a structurally normal heart (most often due to transplacental passage of maternal antibodies in connective tissue disease), and sinus bradycardia in a premorbid fetus. The most common structural defects seen in association with CHB are listed in Table 42-1. Although pregnant women with connective tissue disease are at significantly increased risk for having a fetus with CHB, only 50% of fetuses with bradycardia are born to women with a history of collagen vascular disease (Petri et al., 1989; McCauliffe, 1995). Fetal CHB may be the first manifestation of maternal collagen vascular disease.

A fetus diagnosed early in the development of heart block may present with irregular heart rhythm due to second-degree AV block. This may occur either as partial progressive AV block, (the Wenckebach phenomenon), or as second-degree AV block in which the P–R interval is relatively fixed and the ratio of transmission may be 2:1, 3:1, or 4:1, etc. Schmidt et al. (1991) have observed progression from normal sinus rhythm to second-degree block to CHB.

While bradycardia is well tolerated by most fetuses, nonimmune hydrops will develop in up to 25% as a result of cardiac decompensation (Kleinman et al., 1982; Stewart et al., 1983; Holzgreve and Golbus, 1984; Crowley et al., 1985; Carpenter et al., 1986; Machado et al., 1988). In 90% of cases associated with a structurally normal heart, the infant is born with neonatal lupus erythematosus (McCauliffe, 1995).

Fetal CHB usually presents during the second trimester in the setting of a structurally normal heart. Although fetal CHB has been diagnosed as early as 17 weeks, the mean gestational age at presentation is closer to 26 weeks (Schmidt et al., 1991). There is some evidence to suggest that a progressive rise in transplacental passage of immunoglobulin occurs after 22 weeks’ gestation, which correlates with progressive immune-mediated injury to the fetal conduction system (Stiehm, 1975).