The most common fetal bradyarrhythmia diagnosed prenatally is congenital complete heart block (CHB), usually occurring in association with circulating maternal anti-Ro or anti-La antibodies, but also occurring together with structural fetal cardiac malformation.
Sonographic diagnosis of complete heart block (CHB) is made using M-mode echocardiography, demonstrating complete dissociation between atrial and ventricular rates; varying degrees of cardiac failure and hydrops may also be present.
Immune-mediated CHB usually leads to permanent damage to the fetal cardiac conduction system, and controversy exists as to whether subsequent prenatal therapy by maternal administration of corticosteroids will have any meaningful benefit.
Other options for prenatal therapy include maternal betamimetic administration, although its role is generally limited by maternal side effects; additionally experimental approaches to fetal cardiac pacing have also been described in cases with very poor prognosis.
While vaginal delivery is possible with appropriate intensive fetal surveillance, for practical reasons, most such fetuses are delivered elective by cesarean; delivery should occur in a tertiary care facility with appropriate pediatric cardiology backup available.
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(15%), fetuses with bradyarrhythmia due to complete heart block (CHB) account for 9% of all cases (Kleinman and Evans, unpublished data, 1988).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.
Table 42-1Structural Heart Defects Most Commonly Associated with Fetal Complete Heart Block ||Download (.pdf) Table 42-1 Structural Heart Defects Most Commonly Associated with Fetal Complete Heart Block
|Left atrial isomerism |
|Transposition of the great arteries |
|Atrioventricular septal defect |
|Pulmonic atresia |
|Anomalous pulmonary venous connection |
|Double outlet right ventricle |
|Atrioventricular discordance |
|Absent right atrioventricular connection |
|Double inlet ventricle |
|Right atrial isomerism |
|Pulmonic stenosis |
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.
ANTENATAL NATURAL HISTORY
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).
The majority of the fetuses with CHB tolerate the slower ventricular rate relatively well and progress to term without incident. However, in 15% to 25% of fetuses with CHB nonimmune hydrops will develop and the fetus will die in utero or shortly after delivery. In a multicenter review, Schmidt et al. (1991) found that fetuses with structurally normal hearts and CHB with ventricular rates of less than 55 bpm had only a 14% survival rate. The presence of nonimmune hydrops was a poor prognostic feature, with only a 15% survival rate. Similarly, when CHB complicated structural heart disease, the survival was only 14%. The development of AV valve incompetence is also a harbinger of fetal cardiac decompensation and nonimmune hydrops (Schmidt et al., 1991). AV valve incompetence appears to be due to distortion at the valve rings by progressive ventricular dilation with the slow ventricular rate. In the fetal-sheep model of CHB, slower ventricular rates cause progressive diastolic distention of the ventricles distorting the AV valve rings, resulting in regurgitation (Crombleholme et al., 1991). The AV valve incompetence can be immediately reversed by increasing the ventricular rate by pacing the heart, which reduces the diastolic ventricular distention. AV valve incompetence tends to precede the development of nonimmune hydrops because it results in venous hypertension and passive hepatic congestion, leading to pericardial and pleural effusions, ascites, and anasarca.
In addition to progressive destruction of the fetal conduction system by an inflammatory response to maternal autoantibody deposition, a generalized myocarditis may also be seen in fetal CHB. In these cases, antibody deposition occurs throughout the heart, and the inflammatory reaction results in progressive myocardial decompensation. Subendocardial fibroelastosis may result, which can be an indicator of end-stage myocardial injury. These may appear as echogenic papillary muscles or areas of subendocardial myocardium in the ventricle or atria (Figure 42-1).
Four-chamber view of the heart in a fetuswith complete heart block due to transplacental passage of SSA antibodies in a mother with systemic lupus erythematosis. The atrial rate was 135 beats per minute with a ventricular response rate of 54 beats per minute. There is evidence of endocardial fibroelastosis (EFE) in this heart most notably in the papillary muscle and in the interventricular septum.
A woman with no previous history of collagen vascular disease who presents carrying a fetus with CHB should have a formal rheumatologic evaluation. On close questioning, such women often report dry eyes/mouth or arthralgias, which suggest collagen vascular disease (McCauliffe, 1995). The fetus should undergo a complete anatomic sonographic survey, including Doppler waveform studies of umbilical arterial diastolic flow. Echocardiography should be performed, not only to exclude structural heart disease, but also to confirm AV dissociation and document the atrial and ventricular rates. In addition, assessment of ventricular contractility, presence or absence of increased myocardial echogenicity suggestive of subendocardial fibroelastosis, AV valve incompetence, and stroke volume should be noted and serve as a baseline for comparison with future studies.
The diagnosis of immune-mediated fetal heart block should be treated by maternal steroid administration. During the third trimester there may be progressive slowing of ventricular rate, and increased frequency of surveillance is indicated in fetuses with ventricular rates of less than 65 bpm. Heart rates less than 60 bpm may prompt a twice-weekly ultrasound examination to detect AV valve incompetence or early signs of nonimmune hydrops. Similarly, serial echocardiography is indicated to detect subtle changes in contractility, stroke volume, myocardial echogenicity, and onset of AV valve incompetence. Diastolic flow in the umbilical arteries is also a useful marker to follow because it indicates impedance to flow in the placental circulation. Increased resistance due to deposition of immune complexes in the placental bed may precipitate heart failure. Because of the progressive dilation of heart chambers, cardiothoracic ratios may be useful indicators of possible pulmonary hypoplasia. Because of the lack of heart rate variability, standard nonstress tests are not helpful.
The indications for delivery in fetal CHB include obvious signs of deteriorating cardiac status, with the subsequent development of nonimmune hydrops. The mode of delivery in fetal CHB is controversial. If the fetus is being delivered for signs of cardiac decompensation, the stress of vaginal delivery may cause further hemodynamic compromise (Paladini et al., 1990). In addition, detection of nonreassuring fetal heart rate status in the setting of fetal CHB is very difficult. Some authors have delivered noncompromised fetuses with CHB vaginally, using continuous heart rate monitoring and fetal blood sampling during labor (Olah and Gee, 1993). Some authors have advocated continuous monitoring of ventricular rate by scalp electrodes, atrial rate by external transducers, or fetal pulse oximetry by scalp probes or transcutaneous pCO2 (Todras et al., 1989; Chan et al., 1990a, 1990b). Other authors have suggested continuous intrapartum echocardiography.
While such intensive surveillance is possible, we recommend cesarean delivery for any fetus at more than 30 weeks’ gestation with CHB and evidence of hemodynamic compromise, manifested by nonimmune hydrops, a ventricular rate of less than 55 bpm, AV valve insufficiency, or poor contractility. In fetuses in which CHB is well tolerated, vaginal delivery may be considered, but only if appropriate intrapartum monitoring is available. Delivery should be performed at a center with pediatric cardiologists and surgeons who are available for placement of either temporary transvenous or epicardial pacing leads.
Numerous antenatal treatments, both medical and surgical, have been proposed in the management of the fetus with CHB. The medical therapies are divided into those intended to minimize the immunologic injury to the fetal heart and those geared toward increasing the ventricular rate.
Controversy exists over the prenatal treatment of CHB. The form of treatment used most often is administration of steroids to the mother to limit the fetal inflammatory response (Barclay et al., 1987; Bunyan et al., 1987; Fox and Hawkins, 1990; Jaeggi et al., 2004). Dexamethasone is preferred over prednisone. Because of the fear of adverse side effects due to steroids, such as maternal insulin resistance, lowered resistance to infection, and poor wound healing, some authors have recommended against prophylactic treatment for anti-Ro antibody positive mothers. However, once antibody-mediated damage to the fetal conduction system has occurred, it is permanent. Because myocardial injury is likely permanent at the time of presentation with CHB, it has been argued that there is minimal role for steroid therapy once that stage has been reached.
Jaeggi et al. published a protocol for the management of prenatally diagnosed CHB without structural heart disease (Figure 42-2). This report included 37 patients treated by this approach divided into two groups based on year of diagnosis. Patients received maternal dexamethasone or maternal betamimetics. The survival of the earlier group treated from 1990 to 1996 was 80% at birth and 47% to 1 year of life. In contrast, the more recent group of patients treated between 1997 and 2003 had a survival to birth and 1 year of 95% (p < 0.01). The use of the glucocorticoid dexamethasone appeared to be the primary reason for this improved survival. Among these mothers receiving dexamethasone, the survival was 90% versus 46% without dexamethasone.
Suggested protocol for the management of prenatally diagnosed complete heart block without structural heart disease.
This group therefore recommended maternal dexamethasone administration (4–8 mg/d) and with betamimetics (ritodrine 30–60 mg/d or salbutamol 10 mg/d) for cases in which ventricular response rate is below 55 bpm or in which there is evidence of abnormal ventricular function. In the dexamethasone-treated mother, adverse effects attributed to steroid included oligohydramnios (19%), and one mother developed hypertension. It is unclear whether the addition of betamimetics to dexamethasone conferred any additional benefit. It is possible that in this setting betamimetics either prevented further decrease in heart rate or improved myocardial function. The QT interval should be assessed in all patients prior to starting betamimetics and should be avoided in prolonged QT syndrome. Betamimetics may alter ventricular depolarization and dramatically lengthen QTc that may trigger cardiac events. The use of magnetocardiography may be useful in the diagnosis of prolonged QT syndrome and assist management of CHB (Hosono et al., 2001).
Betamimetic agents, such as terbutaline, ritodrine, and isoproterenol have been used in attempts to accelerate the fetal heart rate (Carpenter et al., 1986; Martin et al., 1988; Schmidt et al., 1991; Jaeggi et al., 2004). The responses to these agents have been variable, and no definite benefit has been proven (Crowley et al., 1985; Carpenter et al., 1986; Machado et al., 1988). In addition, doses sufficient to cause an increase in fetal ventricular rate are often poorly tolerated by the mother.
The use of intravenous immunoglobulin (IVIG) in fetal CHB has been described. IVIG is thought to bind circulating anti-Ro antibody in the maternal circulation to prevent transplacental passage, by increasing immune clearance of the antibody. It may also downregulate anti-Ro antibody production. Limited data are available to support this intervention.
Plasmapheresis has also been recommended to limit cardiac damage once pericardial effusion, heart enlargement, or conduction disturbance develops (Bunyan et al., 1987). However, plasmapheresis cannot reverse fetal CHB once it is established (Heurman and Golezewski, 1985). Bunyan et al. (1988) have suggested that plasmapheresis be used prior to 20 weeks’ gestation, before increased antibody passage occurs across the placenta. This requires plasmapheresis three times a week, in addition to steroid treatment. The use of plasmapheresis is based on the idea of removing maternal anti-Ro antibody and decreasing transplacental passage, although damage to the fetal conduction system might not be reversed using this regimen. None of these immunologic strategies has any proven efficacy in preventing or reversing the consequences of fetal CHB due to anti-Ro antibodies.
Early cesarean delivery for temporary pacemaker placement has been associated with a mortality rate that approaches 80% (Kleinman and Downerstein, 1985; Martin et al., 1988). The lack of effective medical treatment for the fetus with CHB and evidence of cardiac decompensation and poor outcome with early delivery have prompted some groups to attempt pacing the fetal heart in utero (Carpenter et al., 1986; Crombleholme et al., 1989, 1990, 1991; Harrison et al., 1993). While technically successful in individual human and animal model cases, such intervention is still considered experimental.
In order for fetal cardiac pacing to be effective, appropriate case selection is essential. Fetuses without hydrops do not need cardiac pacing. Fetuses with advanced hydrops are unlikely to benefit from cardiac pacing. However, a fetus with CHB with ventricular escape rates of less than 50 bpm despite corticosteroid and betamimetic therapy is at especially high risk. These fetuses should be followed closely for development of early signs of hydrops, such as pericardial or pleural effusion or AV valve insufficiency, which usually precedes hydrops. These fetuses are at high risk, and may be candidates for fetal cardiac pacemaker placement. Open fetal surgery for fetal CHB may be preferable because a percutaneously placed pacing lead may become dislodged, cause cardiac tamponade, chorioamnionitis, or cord enlargement. The contraindications to open fetal surgery for pacemaker placement include uterine irritability, maternal illness, structural fetal heart disease, massive hydrops, or poor ventricular function that is sometimes associated with subendocardial fibroelastosis. It may be reasonable for corticosteroids to be administered to the pregnant woman for fetuses with CHB to minimize ongoing immune-mediated myocardial cardiac injury. While the injury to the fetal conduction system is permanent and irreversible, it is possible that progressive myocarditis may be averted by maternal steroid treatment. Except for one anecdotal case, there are no data to support the use of plasmapheresis in fetal CHB.
Neonatal lupus erythematosus (NLE) is a misnomer, as these newborns do not have systemic lupus erythematosus, but a constellation of clinical disorders associated with, and probably in part caused by, autoantibodies that are passively acquired by the fetus transplacentally (McCauliffe, 1995). The majority of newborns with NLE exhibit cutaneous or cardiac disease (Table 42-2).
Table 42-2Clinical Manifestations of Neonatal Lupus Erythematosus ||Download (.pdf) Table 42-2 Clinical Manifestations of Neonatal Lupus Erythematosus
| System || Description || Presentation |
|Cutaneous ||Erythematous round, oval, and annular patches ||Weeks to months after delivery. Resolves after 6 months, occasional residual pigmentation |
|Cardiac ||Complete heart block, myocarditis, congestive heart failure ||Usually third trimester, but as early as 17 weeks, invisible heart block |
|Hematologic ||Thrombocytopenia, anemia, leukopenia ||At birth, usually self-limited |
|Hepatic ||Hepatomegaly, hepatitis, cholestasis ||At birth, usually self-limited |
In the absence of structural heart disease, the newborn with congenital CHB has NLE, which is associated with a distinctive skin rash of erythematous round eruptions due to antibody disposition on basal keratinocytes (McCauliffe, 1995). This rash may be increased by light exposure, especially phototherapy for hyperbilirubinemia. Parents are advised to keep affected infants out of direct sunlight for the first 6 months of life, after which the NLE resolves. In addition to cardiac and dermatologic manifestations, NLE may present with thrombocytopenia or anemia, as well as hepatosplenomegaly, hepatitis or cholestasis, aseptic meningitis, myopathy, or myasthenia (McCauliffe, 1995).
In the delivery room, an isoproterenol drip should be initiated as soon as intravenous access is secure. Corticosteroids may be administered to prevent ongoing myocardial injury. Some neonatologists have performed exchange transfusions to eliminate circulating maternal antibody, but no data are available to support its use. Cardiac pacing is the definitive treatment. If the child is unstable or delivered for cardiac decompensation, a transvenous or transthoracic temporary pacing lead should be placed. This may not be possible in a premature infant, in whom a left anterior thoracotomy for placement of temporary epicardial pacing leads should be performed until the infant is sufficiently large to undergo permanent placement of a cardiac pacemaker. If the fetus is hydropic, delivered for cardiac decompensation, or has a ventricular rate less than 55 bpm, some form of cardiac pacemaker should be placed urgently. The degree of heart block is permanent and if the heart is decompensating, medical therapy such as isoproterenol is unlikely to prevent progressive deterioration.
The mortality rate for infants presenting in the newborn period with CHB is at least 25%. In a long-term follow-up study Vetter and Rashkind (1983) documented 90% survival after the neonatal period. Most deaths were due to pacemaker failure. These children need to be followed for the later development of rheumatologic disease. McCauliffe, (1995) described seven patients with congenital CHB who went on to develop collagen vascular diseases, either systemic lupus erythematosus or Sjögren syndrome. Whether this is due to NLE is unknown. More likely, this represents familial predisposition or inheritance of an HLA type associated with collagen vascular disease.
GENETICS AND RECURRENCE RISK
There is no known genetic predisposition for the development of fetal CHB. The woman who has previously had a fetus with NLE is at greatest risk for recurrence. The manifestations of NLE tend to be the same in subsequent pregnancies. Petri et al. (1989) found that mothers of infants with NLE manifested by CHB had a 64% chance of a subsequent fetus being similarly affected. However, McCune et al. (1987) found only a 25% recurrence of CHB.
Women with a history of an autoimmune disorder and anti-Ro antibodies constitute the next highest risk category. Ramsey-Goldman et al. (1986) found that only 8% of infants born to mothers with SLE who had anti-Ro antibodies were affected by NLE. Among mothers with SLE but no anti-Ro antibodies, the incidence of NLE was only 0.6%. Normal women, or those with ill-defined symptoms who produce anti-Ro antibodies, are probably at even lower risk. Unfortunately, this latter category accounts for 50% of cases of NLE, which are impossible to identify before the fetus or newborn is symptomatic (Petri et al., 1989; McCauliffe, 1995).
Olah and Gee, (1993) have defined four known risk factors: a previous child with CHB, a high titer of anti-Ro antibody (>1:16), presence of anti-La antibody in addition to anti-Ro antibody, and maternal HLA-DR3.
et al.. Anti-Ro/SS-A antigens in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. Arthritis Rheum. 1992;35:176-–189.
et al.. Evolution of fetal arrhythmias by echocardiography. Br Heart J. 1983;50:240-–245.
et al.. Echocardiographic and anatomic correlates in fetal congenital heart disease. Br Heart J. 1984a;52:542-–548.CrossRef
et al.. Successful pregnancy following steroid therapy and plasma exchange in a woman with anti-Ro (SS-A) antibodies: case report. Br J Obstet Gynaecol. 1987;94:369-–371.
et al.. Complete congenital heart block: risk of occurrence and therapeutic approach to prevention. J Rheumatol. 1988;15:1104-–1108.
et al.. Intrauterine therapy for presumptive fetal myocarditis with acquired heart block due to systemic lupus erythematosus. Arthritis Rheum. 1987;30:44-–49.
CA. Diagnosis and management of fetal cardiac dysrhythmia. Contemp Rev Obstet Gynaecol. 1989;1:195-–199.
et al.. Fetal ventricular pacing for hydrops secondary to complete AV block. J Am Coll Cardiol. 1986;8:1434-–1436.
et al.. Simultaneous pulsed Doppler velocimetry of fetal aorta and inferior vena cava: diagnosis of fetal congenital heart block: two case reports. Eur J Obstet Gynecol Reprod Biol. 1990a;35:89-–95.CrossRef
et al.. Prenatal diagnosis of congenital fetal arrhythmias by simultaneous pulsed Doppler velocimetry of the fetal abdominal aorta and inferior vena cava. Obstet Gynecol. 1990b;76:200-–204.
LD. The assessment of persistent bradycardia in prenatal life. Br J Obstet Gynaecol. 1985;92:941-–944.
et al.. CHB in fetal lambs. I. Technique and acute physiologic response. J Pediatr Surg. 1990;25:587-–593.
et al.. CHB and AV-sequential pacing in fetal lambs: the atrial contribution to combined ventricular output in the fetus. Surg Forum. 1989;40:268-–270.
et al.. A model of nonimmune hydrops on fetal lambs: CHB-induced hydrops fetalis. Surg Forum. 1991;42:487-–489.
et al.. Two-dimensional M-mode echocardiographic evaluation of fetal arrhythmias. Clin Cardiol. 1983;51:237-–243.
et al.. Two-dimensional and M-mode echocardiographic evaluation of fetal arrhythmias. Clin Cardiol. 1985;8:1-–6.
et al.. Localization of Ro (SS-A) antigen in the cardiac conduction system. Arthritis Rheum. 1987;30:1232-–1238.
LD. Fetal echocardiography. III. M-mode ultrasound. Am J Obstet Gynecol. 1983;146:792-–799.
DF. Fetal pericardial effusion in association with congenital heart block and maternal systemic lupus erythematosus: case report. Br J Obstet Gynaecol. 1990;97:636-–640.
et al.. Autoantibodies directed against sicca syndrome antigens in the neonatal lupus syndrome. J Am Acad Dermatol. 1981;4:67-–72.
SH. Congenital heart block. Am J Obstet Gynecol. 1984;88:238-–241.
et al.. Placental abnormalities in systemic lupus erythematosus: in-situ deposition of antinuclear antibodies. J Rheumatol. 1987;14:924-–929.
et al.. Ro (SS-A) antibody and antigen in a patient with congenital CHB. Arthritis Rheum. 1985;28:1321-–1325.
et al.. Ro and La antigens and maternal anti-La idiotypes on the surface of myocardial fibers in congenital heart block. J Radiol. 1991;4:165-–176.
N. Maternal connective tissue disease and congenital heart block. N Engl J Med. 1985;312-–329.
et al.. Investigation of non-immune hydrops fetalis. Am J Obstet Gynecol. 1984;150:805-–812.
T. A case of fetal complete heart block recorded by magnetocardiography, ultrasonography and direct fetal electrocardiography. Fetal Diagn Ther. 2001;16(1):38-–41.CrossRef
et al.. Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation. 2004;110:1542-–1548.
T. Neonatal lupus erythematosus: new serologic finding. J Invest Dermatol. 1981;77:331-–333.
RL. Ultrasonic assessment of cardiac function in the intact human fetus. J Am Coll Cardiol. 1985;7(suppl 1.): 843-–845.
et al.. Fetal echocardiography for the evaluation of fetal CHF. N Engl J Med. 1982;306:568-–575.
et al.. Echocardiographic studies of the human fetus: prenatal diagnosis of congenital heart disease and cardiac dysrhythmias. Pediatrics. 1980;65:1059-–1066.
et al.. Cardiac immunoglobulin deposition in congenital heart block associated with maternal anti-Ro autoantibodies. Am J Med. 1987;83:793-–796.
et al.. Maternal connective tissue disease and congenital heart block: demonstration of immunoglobulin in cardiac tissue. N Engl J Med. 1985;312:98-–100.
et al.. Successful management of congenital AV block associated with hydrops fetalis. J Pediatr. 1988;112:984-–986.
DP. Neonatal lupus erythematosus: a transplacentally acquired autoimmune disorder. Semin Dermatol. 1995;14:47-–53.
et al.. Congenital heart block in newborns of mothers with connective tissue disease. Circulation. 1977;56:82-–90.
LA. Maternal and fetal outcome in neonatal lupus erythematosus. Ann Intern Med. 1987;106:518-–523.
GG. Congenital CHB in newborns, infants, children, and adults. Med Times. 1969;97:113-–123.
MA. Congenital CHB: an international study of the natural history. Pediatr Cardiol. 1972;4:87-–101.
et al.. Placental transfer of anti-cytoplasmic antibodies in annular erythema of newborns. Arch Dermatol. 1981;717:569-–572.CrossRef
H. Monitoring the fetus with congenital heart block—the use of the first-interval resistance index. J Perinatol Med. 1991;19(suppl s):211.
H. Antibody mediated complete congenital heart block in the fetus. Pacing Clin Electrophysiol. 1993;16:1872-–1879.
LD. Prenatal measurement of cardiothoracic ration in evaluation of heart disease. Arch Dis Child. 1990;65:20-–23.
et al.. Cytomegalovirus infection in pregnancy: preliminary findings from a prospective study. Lancet. 1983;1:1352-–1355.
MC. Anti-Ro antibodies and neonatal lupus. Rheum Dis Clin North Am. 1989;15:335-–360.
et al.. Anti-SS-A antibodies and fetal outcome in maternal systemic lupus erythematosus. Arthritis Rheum. 1986;29:1269-–1273.
et al.. Perinatal outcome of fetal complete AV block: a multi-center experience. J Am Coll Cardiol. 1991;17:1360-–1366.
et al.. Connective tissue disease, antibodies to ribonucleoprotein and congenital heart block. N Engl J Med. 1983;309:209-–212.
et al.. Arrhythmia and structural abnormalities of the fetal heart. Br Heart J. 1983;50:550-–554.
EF. Fetal defense mechanisms. Am J Dis Child. 1975;129:438-–443.
M. Fetal Doppler echocardiographic assessment of cardiac blood flow velocity in normal fetuses and those with congenital heart disease. Nippon Sanka Fujinka Gakkai Zasshi. 1989;41:211-–216.
et al.. Maternal antibodies against fetal cardiac antigens in congenital CHB. N Eng J Med. 1988;315:667-–672.CrossRef
JC. Antenatal diagnosis of congenital heart block: report of a case. Obstet Gynecol. 1979;32:851-–853.
et al.. Conservative management of fetal beginning arrhythmia leading to persistent bradycardia. Eur J Obstet Gynecol Reprod Biol. 1989;34:211-–215.CrossRef
M. Evaluation of the human fetal cardiac size and function. Am J Perinatol. 1990;7:54-–59.CrossRef
RN. Purification and characterization of the SjÖgren's syndrome A and B antigens. Clin Exp Immunol. 1983;54:731-–738.
JA. The Ro small cytoplasmic ribonucleoproteins: identification of the antigenic protein and its binding site on the Ro RNAs. Proc Natl Acad Sci U S A. 1984;81:1966-–2000.