Ineffective Therapy, Underpowered Studies, or Merely Too Little, Too Late?

Abstract

It is estimated that 2% to 3% of pregnant women carry the anti-SSA/Ro antibody, which can be found in various autoimmune disorders, including Sjogren syndrome (SS), systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disorder.1,2 In addition, many women are asymptomatic carriers, with less than one third of anti-SSA/Ro–positive women diagnosed with a rheumatological disorder preceding the discovery of advanced heart block in the fetus.3,4 Prospective studies have demonstrated that, in the absence of a previously affected pregnancy, the fetuses of these women bear up to a 3% risk of developing cardiac manifestations of neonatal lupus (NL), including cardiac conduction abnormalities, structural cardiac defects, and isolated cardiomyopathies.5–7 In women with a previously affected pregnancy, the recurrence rate of congenital heart block can reach as high as 17%.8,9 Articles see p 1919 and p 1927 The cardiac conduction manifestations of NL are thought to result from a pathological response to the transplacental acquisition of anti-SSA/Ro whereby an immune-mediated inflammatory pathway triggers injury and eventually fibrosis of the atrioventricular (AV) node.10 In addition, anti-SSA/Ro antibodies appear to inhibit activation of the cardiac L-type calcium channels, which are essential to normal AV node conduction.11 The role of anti-SSB/La antibodies is less clearly defined. Although anti-SSB/La alone has not been associated with conduction abnormalities, some evidence suggests that it may potentiate the effects of anti-SSA/Ro–mediated injury.12 Antibody-exposed infants without cardiac involvement at birth have little risk of later developing AV block; however, complete AV block can evolve in fetuses with second-degree AV block in utero or neonates born with first- or second-degree AV block.9 Jaeggi and colleagues3 reported that the timing of initial presentation of complete AV block correlated with mortality. Among the 29 cases diagnosed …