Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block: Results of a multicenter, prospective, open‐label clinical trial

Abstract

Objective The recurrence rate of anti-SSA/Ro associated congenital heart block (CHB) is 17%. Reversal of 3rd degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, IVIG was evaluated as a preventative therapy for CHB. Methods A multicenter open-label study based on Simon’s 2-stage optimal design was initiated. Enrollment criteria included: maternal anti-SSA/Ro antibody, a previous child with CHB/rash, </= 20 mg prednisone, < 12 weeks pregnant. IVIG (400mg/kg) was given every 3 weeks from 12 to 24 weeks of gestation. The primary outcome was the development of 2nd or 3rd degree CHB. Results Twenty mothers completed the IVIG protocol before reaching the pre-determined stopping rule of three cases of advanced CHB. CHB was detected at 19, 20 and 25 weeks; none followed an abnormal PR interval. One of these mothers had two previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal antibody titers to SSA/Ro, SSB/La, or Ro52 were detected over the course of therapy or at delivery. There were no safety issues. Conclusions IVIG at doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers. Having established safety with this protocol and feasibility of patient enrollment, subsequent preventative studies may be considered, perhaps to include higher doses of IVIG.

Evaluation of Transplacental Treatment for Fetal Congenital Bradyarrhythmia

“…immunoglobulins are not beneficial for preventing progression to congenital AVB. 33, 34 Similarly, the present study found a lack of superiority of transplacental treatment for second-degree AVB with bradyarrhythmia.…”

Recurrent second-trimester intrauterine fetal death due to undiagnosed atrioventricular block: A case report

“…15 Friedman et al documented cure of second-degree atrioventricular block in two of six fetuses treated with corticosteroids, but in spite of this treatment, three of the fetuses (50%) progressed to complete atrioventricular block (one intrauterine, two after delivery). 19 The incidence of fetal atrioventricular block is about 2% of pregnancies in females with SSA/ Ro or SSB/La autoantibodies. 18 Serial echocardiography screening is not helpful because there has been no evidence that this prevented the development of atrioventricular block.…”

“…The risk of recurrent atrioventricular block when a previous fetus has been affected is about 19%. 19 The most serious complication seen in females with positive antibodies is the occurrence of repolarization abnormalities and this may increase the incidence of sudden cardiac arrest documented in this group of patients. 20 In a females with SSA/Ro-related fetal cardiac complications, follow-up with FMCG is highly recommended to assess depolarization and repolarization anomalies, confirm the degree of block, and evaluate myocardial hypertrophy 21,22 but, this method is still not readily accessible to doctors in most centers.…”

“…If FMCG is not available, such females should be followed up with fetal echocardiography to measure mechanical PR interval and to detect signs of endocardial fibroelastosis, tricuspid valve regurgitation, cardiac dysfunction, or atrioventricular block. 19 Subsequently repolarization abnormalities cannot be documented without FECG or FMCG.…”

Neonatal lupus

“…Приблизительно у 1-3% плодов и новорожденных от матерей, позитивных по Ro/SSA-и La/SSB-антителам, раз-вивается ВППБ. При последующих беременностях риск этой патологии возрастает до 17-18% [35][36][37].…”