Failure of intravenous immunoglobulin to prevent congenital heart block: Findings of a multicenter, prospective, observational study

Abstract

Objective. Congenital heart block (CHB) is presumed to be caused by transplacental passage of maternal immunoglobulin against Ro and La ribonucleoproteins. The recurrence rate in subsequent pregnancies following the birth of a child with CHB is ϳ19%. The purpose of this study was to determine whether intravenous immunoglobulin (IVIG) therapy could prevent the development of CHB in the fetuses of high-risk pregnant women.Methods. A total of 24 pregnancies in 22 women who had a previous pregnancy in which CHB developed, were over the age of 18 years, were <12 weeks pregnant, and had anti-Ro, anti-La, or both antibodies were monitored in this multicenter, prospective, observational study. Fifteen patients received infusions of IVIG. The 9 pregnancies in the remaining 7 patients served as controls. IVIG was administered at a dose of 400 mg/kg at weeks 12, 15, 18, 21, and 24 of pregnancy. Echocardiograms were performed at least every 3 weeks from week 15 to week 30 of gestation. Electrocardiograms were obtained at birth. The outcome measure was the development of third-degree CHB detected by fetal echocardiogram.Results. CHB developed in 3 babies among the 15 pregnancies in the treatment group (20%) and in 1 baby among the 9 pregnancies in the control group (11%). CHB was detected at weeks 18, 23, and 26, respectively, in the 3 babies in the treated group and at week 19 in the baby in the control group. Three of the affected pregnancies ended in termination; 2 for reasons related to the fetal disease and 1 for reasons related to both maternal (severe pulmonary hypertension) and fetal disease (at 21 weeks of gestation).Conclusion. IVIG at the dose and frequency used in this study was not effective as prophylactic therapy for CHB in high-risk mothers.Congenital heart block (CHB) is a model of passive autoimmunity that is presumed to be caused by transplacental passage of maternal immunoglobulin (IgG) against Ro and La ribonucleoproteins (1). The incidence of CHB in the offspring of mothers with the pathologic autoantibodies ranges between 1% and 2% (2,3). The recurrence rate in subsequent pregnancies following the birth of a child with CHB is ϳ19%, and the development of CHB subsequent to the birth of a child with a neonatal lupus rash is ϳ24% (4,5). The presence of maternal antibodies is necessary, but not sufficient, to cause CHB. The uterine environment, fetal factors (e.g., genes, viral infections), and maternal factors (e.g., specific autoantibody profile, such as reactivity to peptide 200-239 [p200] of Ro 52 kd) (6) have been postulated as possible cofactors in the development of CHB.

Autoantibodies in Heart Failure and Cardiac Dysfunction

“…120 The potential of IVIG to prevent CHF and to reduce proinflammatory cytokines has been shown in an experimental model of virus induced autoimmune myocarditis in experimental Chagas disease and in human DCM. [121][122][123][124][125][126] IVIG preparations are believed to bind to and neutralize circulating autoantibodies of diverse specifity.…”

Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome

“…International efforts have attempted to improve the understanding and management of this condition, with major contributions from different groups [8,12,[14][15][16][17][18][19]. However, registries are needed to improve our knowledge and the management of CHB.…”

Atrioventricular Block

“…Two recent multicenter prospective studies (one in Europe and one in the United States) demonstrated that IVIG given to mothers with a previous child with congenital AV block could not prevent recurrence of CAVB. 14,15 Most recently, a multicenter case-control study found that hydroxychloroquine, given to mothers with a previous child with cardiac neonatal lupus,…”