Prevention and Treatment In Utero of Autoimmune-Associated Congenital Heart Block

Abstract

Transplacental transfer of maternal anti-Ro and/or anti-La autoantibodies can result in fetal cardiac disease including congenital heart block and cardiomyopathy, called cardiac Neonatal Lupus (NL). Thousands of women are faced with the risk of cardiac NL in their offspring, which is associated with significant morbidity and mortality. There are no known therapies to permanently reverse third degree heart block in NL, although several treatments have shown some effectiveness in incomplete heart block and disease beyond the atrioventricular node. Fluorinated steroids taken during pregnancy have shown benefit in these situations, although adverse effects may be concerning. Published data are discordant on the efficacy of fluorinated steroids in the prevention of mortality in cardiac NL. β-agonists have been used to increase fetal heart rates in utero. The endurance of β-agonist effect and its impact on mortality are in question, but when used in combination with other therapies, they may provide benefit. No controlled experiments regarding the use of plasmapheresis in cardiac NL have been performed, despite its theoretical benefits. Intravenous immunoglobulin was not shown to prevent cardiac NL at a dose of 400 mg/kg, although it has shown effectiveness in the treatment of associated cardiomyopathy both in utero and after birth. Retrospective studies have shown that hydroxychloroquine may prevent the recurrence of cardiac NL in families with a previously affected child, and a prospective open-label trial is currently recruiting patients in order to fully evaluate this relationship.

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

“…As regularly emphasized [21][22][23], the management of CHB remains questionable and controversial, especially regarding the use of fluorinated steroids. In our series, 39.1% of cases received fluorinated steroids versus 38% and 47.8%, respectively, in the European/Brazilian and US registries.…”

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome

“…Moreover, there is no proven efficacy of protocols for the prevention or treatment of complete CHB. 99 100 The efficacy of maternal fluorinated steroids has not been established in large cohorts [101][102][103][104] despite initial reports of favourable effects in cases of incomplete CHB, cardiomyopathy, endocardial fibroelastosis and hydrops fetalis. 99 Given the potential of fluorinated steroids for major maternal and fetal side effects, the benefit for fetuses with CHB should be stratified according to the presence of risk factors for adverse outcome.…”

Bloqueo auriculoventricular fetal completo: enfoque diagnóstico y terapéutico; reporte de caso en Bogotá, Colombia y revisión de la literatura

“…Los esteroides fluorados como la betametasona y dexametasona, al atravesar la barrera placentaria ingresan a la circulación fetal y mitigan la inflamación cardiaca provocada por los anticuerpos maternos mejorando la contractilidad cardiaca (14,15,20,21), por lo que son los más utilizados ante bloqueos grados I y II según una revisión de la literatura (20). No obstante, esta misma revisión advierte que este grupo de medicamentos cada vez se utiliza menos debido a los reportes de efectos adversos fetales como insuficiencia adrenal, y neonatales como la alteración del crecimiento y del neurodesarrollo.…”

“…Weber et al recomiendan 8 mg/día de dexametasona por dos semanas, posteriormente se disminuye la dosis a 4 mg/día por dos semanas o se administran 2 mg/día si el embarazo es mayor a 28 semanas (21). Se ha reportado mejoría en supervivencia por encima del 90 % con el uso de beta agonistas (principalmente de terbutalina) en los casos de frecuencia cardiaca fetal menor a 55 lpm, ante la presencia de fibroelastosis, hidrops, o en casos en donde hay progresión del bloqueo (14,20).…”