Pediatric Cardiology The Importance of the Level of Maternal Anti-Ro/SSA Antibodies as a Prognostic Marker of the Development of Cardiac Neonatal Lupus Erythematosus A Prospective Study of 186 Antibody-Exposed Fetuses and Infants Edgar Jaeggi, MD,*§ Carl Laskin, MD,† Robert Hamilton, MD,*§ John Kingdom, MD,† Earl Silverman, MD†‡ Toronto, Ontario, Canada Objectives The purpose of this study was to determine whether cardiac complications of neonatal lupus erythematosus (NLE) are related to maternal anti-Ro and anti-La autoantibody-levels. Background Autoantibody-positive mothers are frequently referred for serial echocardiography because of the elevated fetal risk of developing immune-mediated heart block. Little is known why only some and not all offspring are affected. Methods All cases referred since 2000 for serial fetal echocardiography or cardiac complications related to maternal anti- bodies were included. Patients without cardiac NLE (group 1) and with cardiac NLE (group 2) were compared. Antibody levels were measured by enzyme-linked immunosorbent assay with a cutoff value of 8 U/ml for a posi- tive test result. Results Group 1 included 146 serially screened fetuses with normal pregnancy outcomes. Group 2 consisted of 40 fetuses/neonates with a diagnosis of heart block or endocardial fibroelastosis or both, and included 4 fetuses diagnosed during serial screening. All cardiac complications were associated with moderate (50 U/ml; 15%) or high (100 U/ml; 85%) maternal anti-Ro levels, independently of anti-La antibody titres. The event rate of com- plete heart block was 5% for prospectively screened fetuses with Ro-values 50 U/ml (odds ratio: 7.8) and 0% for fetuses with lower titres (p  0.0001). Infants with pre-natal exposure to high-titre anti-La levels 100 U/ml were the most likely to have noncardiac features of NLE (event rate: 57%; odds ratio: 4.7). Conclusions Our findings support that the amount of maternal antibodies, rather than their presence, is associated with fetal tissue injury. As anti-Ro levels correlate with the risk of cardiac complications, serial echocardiography should be limited to women with high anti-Ro-titres. (J Am Coll Cardiol 2010;55:2778–84) © 2010 by the American College of Cardiology Foundation Isolated congenital complete atrioventricular block (CAVB) has been recognized as a distinct clinical entity for 100 years. It was only in the 1950s that it was recognized that maternal autoantibodies will cross the placenta and that fetuses of mothers with an autoimmune disease may develop CAVB (1,2). It took another 20 years before this association became well recognized (3–5) and until the early 1980s that studies documented a close association between maternal anti-Ro/SSA and anti-La/SSB antibodies and congenital heart block (6,7). It was subsequently shown that the highest relative risks of CAVB were seen in offspring of mothers with antibodies against 52-kD Ro and 48-kD La proteins (8,9). The current hypothesis is that maternal antibodies with specificities to the Ro-particle cross the placenta and likely initiate the inflammation of the atrioventricular (AV) node and the myocardium in the susceptible fetus. Subsequent replacement of inflamed tissue with fibrosis will lead to heart block, myocardial dysfunction, and/or endocardial fibroelastosis (EFE) (10,11). The most common time of antibody-mediated fetal cardiac manifestations to be initially detected is between 20 and 24 gestational weeks From the Divisions of *Cardiology and †Rheumatology, Departments of Pediatrics and Immunology, The Hospital for Sick Children, Toronto, Ontario, Canada; ‡The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; and the §Departments of Medicine and Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. Dr. Silverman is on the advisory board of Abbott Canada and Amgen/Wyeth Canada. Manuscript received October 15, 2009; revised manuscript received January 19, 2010, accepted February 15, 2010. Journal of the American College of Cardiology Vol. 55, No. 24, 2010 © 2010 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2010.02.042