Complete heart block, hepatobiliary disease, malar rash, thrombocytopenia and, less frequently, myocarditis comprise neonatal lupus primarily presenting in utero or in the neonate. Frequently, the only manifestation of neonatal lupus, and by extension an autoimmune abnormality in the mother, is CHB in the newborn. Since skin, liver, and blood cells regenerate, the effect of passively acquired antibodies in these organs in the fetus/newborn resolves, usually in the first 6 months of life. However, cardiac cells are not regenerative and thus CHB from neonatal lupus is permanent.

In the absence of congenital heart disease, neonatal lupus is responsible for 60–90 % of cases of congenital CHB. Maternal IgG auto-antibodies to SSA/Ro and/or SSB/La from a mother with an autoimmune connective tissue disorder, most frequently lupus erythematosus, cross the placenta to the fetus during the first trimester. Anti-Ro/SSA and/or anti-La/SSB antibodies bind to fetal cardiac tissue, leading to immune-mediated injury to the AV node and its surrounding tissue.

Both Ro/SSA and La/SSB antigens are abundant in fetal heart tissue between 18 and 24 weeks. Apoptosis induces translocation of Ro/SSA and La/SSB to the surface of fetal cardiomyocytes; the maternal, transplacental anti-Ro and anti-La antibodies then bind to the surface of the fetal cardiomyocytes and induce the release of tumor necrosis factor by macrophages, resulting in fibrosis. In addition to inducing tissue damage, anti-Ro/SSA and/or anti-La/SSB antibodies inhibit calcium channel activation of the cardiac L- and T-type calcium channels themselves; L-type channels allow action potential propagation and conduction in the AV node. The sinoatrial (SA) node also may be involved; sinus bradycardia has been described in 3.8 % percent of fetuses but is usually not permanent.

Immune-mediated CHB accounts for almost all cases of CHB presenting in utero or during the neonatal period. Rarely, it may explain a few cases occurring later (approximately 5 %). Approximately 2 % of babies born to SSA/SSB + mothers, the majority of whom are often asymptomatic, have CHB; however, the recurrence rate for future offspring may be as high as 17 %.

The patients with the neonatal lupus syndrome tend to present earlier than those with CHB not due to neonatal lupus.

Congenital CHB may present with fetal bradycardia between 18 and 28 weeks of gestation. In utero detection is made by echocardiography, which can estimate the fetal PR interval. Complications of CHB in utero include hydrops fetalis, myocarditis, endocardial fibroelastosis, pericardial effusion, and spontaneous intrauterine fetal death. Advanced AV block and cardiomyopathy can occur within one week of normal fetal echo without first-degree AVB (Fig. 16.2).

Infants who present with heart block in utero, but who survive until birth, have a high neonatal mortality rate. In one report, 6 of 22 such infants (27 %) died within one week of birth. In another series, 10 of 107 (9 %) died within the first 3 months. Infants born before 34 weeks have a higher mortality rate than those born later (52 % vs. 9 %). Infants with first- or second-degree heart block at birth can progress to CHB.

As in the fetus, the cardinal finding of CHB in the neonate is a slow heart rate. In addition to bradycardia, other clinical clues in the neonate include intermittent cannon waves in the neck, a first heart sound that varies in intensity, and intermittent gallops and murmurs. As with cases presenting in utero, almost all presenting in the neonatal period are immune mediated. The newborn at greatest risk has a rapid atrial rate, often 150 bpm or faster, and a ventricular rate less than 50 bpm.

Similar to acquired CHB, the ECG most commonly shows a narrow QRS complex due to a junctional escape rhythm. First- or second-degree heart block found in infants at birth can progress to CHB. The outcome for patients diagnosed as neonates is better than for those diagnosed in utero.

As many as 40 % of cases of CHB do not present until childhood (mean age 5 to 6 years) (Fig. 16.3). Few of these patients have neonatal lupus. The diagnosis is usually made when detecting a slow pulse or by presentation with fatigue or syncope, though syncope can herald a more ominous course.

Complete heart block may be intermittent when first detected, but usually becomes persistent in later childhood. It was once presumed that most unexplained CHB diagnosed for the first time beyond infancy was congenital in origin and has escaped notice because of a higher ventricular rate and the absence of symptoms. However, given that prenatal ultrasound is now well developed and in wide use, it appears that cases not detected in fetal life, in fact have preserved AV conduction at birth and acquire progressive AV nodal disease thereafter. Findings from different centers are consistent with the notion of progressive AV nodal disease. In one report, the number of childhood case referrals remained constant from 1980 to 1998 despite the introduction of fetal echocardiography and the wide availability of heart rate monitoring during pregnancy and labor. Second, in a series of 102 patients who were asymptomatic through age 15 and were followed for 7–30 years thereafter, a slow decline in ventricular rate was noted with increasing age. Some patients present with bradycardia-related symptoms, including reduced exercise tolerance, presyncope, or syncope. Sudden death has also been described.