Identification and management of fetuses at risk for, or affected by, congenital heart block associated with autoantibodies to SSA (Ro), SSB (La), or an HsEg5-like autoantigen

Abstract

The congenital heart block (CHB), diagnosed in structurally normal hearts, is strongly associated with, if not caused by, maternal SSA/SSB antibodies (Abs). It develops between 16 and 24 weeks' gestation, coincidentally with the increased transplacental IgG passage, and a window of unique cardiac vulnerability. Less is known about rare CHB cases in which neither cardiac malformations nor SSA/SSB Abs are detectable. We report on four pregnant women: patient 1 at high CHB risk (owing to Sjögren's syndrome (SS) and recurrent pregnancy losses), and patients 2-4 with already established CHB (aggravated by hydrops in patient 2). Abs were found directed to SSA/SSB (patients 1-3) or to an HsEg5-like autoantigen instead (patient 4). During preventive immunoadsorption (IA) from week 19 throughout (patient 1), or therapeutic IA (plus dexamethasone), commenced at week 25 (patient 2), SSA Ab levels decreased per session by 47+/-7 or 80+/-16%, respectively, and hydropic changes resolved. Patient 1 delivered a healthy boy, while patients 2-4 gave birth to CHB-affected children at need for permanent pacing. The irreversibility of complete CHB may justify (a) early ANA screening in all pregnancies (thereby also considering specificities as anti-HsEg5), and (b) preventive immmunoadsorption in high-risk pregnancies (before/during the critical cardiac development phase). This implies controversy, because factors converting risk to disease (in only approximately 2%) are unknown, and prospective randomized treatment studies are not available, given the rarity of CHB.

The Importance of the Level of Maternal Anti-Ro/SSA Antibodies as a Prognostic Marker of the Development of Cardiac Neonatal Lupus Erythematosus

“…We have again shown that most mothers who have a pregnancy complicated by significant fetal cardiac involvement are not identified before the pregnancy because they do not a have connective tissue disease and thus are not referred for prospective fetal evaluation. Consequently, to improve the yield of early detection before CAVB, we agree with a previous suggestion that a successful program to prevent severe cardiac complications would require the screening for anti-Ro antibodies of all pregnant women irrespective of their symptoms or clinical status (33).…”

Pregnancy With SLE and Fetal Congenital Heart Block: A Case Report

“…These autoantibodies damage the AV conduction tissue possibly by inflammation or direct ion channel interaction in the early stage and later by fibrosis [3-5]. The prognosis of isolated congenital heart block in patients presenting as fetuses or at birth is associated with higher morbidity and mortality rates (which may be as high as 30-50%) [6].…”

Clinical and Pathological Roles of Ro/SSA Autoantibody System

“…As most mothers of neonates with NLE do not have any connective tissue disease, a previous suggestion that all pregnant women should be screened for anti-Ro antibodies irrespective of their symptoms or clinical status may be considered reasonable [138]. …”