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

New York Medical College, Valhalla, NY, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 04/2010; 62(4):1138-46. DOI: 10.1002/art.27308
Source: PubMed


The recurrence rate of anti-SSA/Ro-associated congenital heart block (CHB) is 17%. Sustained reversal of third-degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, intravenous immunoglobulin (IVIG) was evaluated as preventive therapy for CHB.
A multicenter, prospective, open-label study based on Simon's 2-stage optimal design was initiated. Enrollment criteria included the presence of anti-SSA/Ro antibodies in the mother, birth of a previous child with CHB/neonatal lupus rash, current treatment with < or = 20 mg/day of prednisone, and <12 weeks pregnant. IVIG (400 mg/kg) was given every 3 weeks from week 12 to week 24 of gestation. The primary outcome was the development of second-degree or third-degree CHB.
Twenty mothers completed the IVIG protocol before the predetermined stopping rule of 3 cases of advanced CHB in the study was reached. CHB was detected at 19, 20, and 25 weeks; none of the cases occurred following the finding of an abnormal PR interval on fetal Doppler monitoring. One of these mothers had 2 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 titers of antibody to SSA/Ro, SSB/La, or Ro 52 kd were detected over the course of therapy or at delivery. There were no safety issues.
This study establishes the safety of IVIG and the feasibility of recruiting pregnant women who have previously had a child with CHB. However, IVIG at low doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers.

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    • "Lorsqu'une femme a eu un enfant avec BAVc, le risque de récurrence du BAVc lors d'une grossesse ultérieure est de l'ordre de 19 % (données sur 257 grossesses issues des observatoires américain, franç ais et d'une série européenne) [15]. Le risque était de 16 % dans deux séries prospectives de 44 grossesses [16] [17]. Le risque d'avoir une manifestation de LN quelle qu'elle soit est estimé à 22 % sur des données rétrospectives [7] "
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    ABSTRACT: Neonatal lupus syndrome is associated with transplacental passage of maternal anti-SSA/Ro and anti-SSB/La antibodies. Children display cutaneous, hematological, liver or cardiac features. Cardiac manifestations include congenital heart block (CHB); endocardial fibroelastosis and dilated cardiomyopathy. The prevalence of CHB in newborns of anti-Ro/SSA positive women with known connective tissue disease is between 1 and 2 % and the risk of recurrence is around 19 %. Skin and systemic lesions are transient, whereas CHB is definitive and associated with significant morbidity and a mortality of 18 %. A pacemaker must be implanted in 2/3 of cases. Myocarditis may be associated or appear secondly. Mothers of children with CHB are usually asymptomatic or display Sjogren's syndrome or undifferentiated connective tissue disease. In anti-Ro/SSA positive pregnant women, fetal echocardiography should be performed at least every 2 weeks from the 16th to 24th week gestation. An electrocardiogram should be performed for all newborn babies. The benefit of fluorinated corticosteroid therapy for CHB detected in utero remains unclear. Maternal use of hydroxychloroquine may be associated with a decreased recurrent CHB risk in a subsequent offspring. A prospective study is actually ongoing to confirm these findings.
    Full-text · Article · Sep 2014
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    • "The risk is five to tenfold higher in women who previously had an affected child with either CHB or a neonatal lupus rash [1] [2]. Fetuses with CHB carry high rates of mortality (20%) and morbidity (>60% of the surviving children require a permanent pacemaker in adulthood) [3] [4]. "
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    ABSTRACT: Background: The presence of anti-SSA/Ro and anti-SSB/La antibodies during pregnancy is associated with fetal congenital heart block (CHB), which is primarily diagnosed through fetal echocardiography. Conclusive information about the complete electrophysiology of the fetal cardiac conducting system is still lacking. In addition to echocardiography, fetal magnetocardiography (fMCG) can be used. fMCG is the magnetic analogue of the fetal electrocardiogram (ECG). Patients and methods: Forty-eight pregnant women were enrolled in an observational study; 16 of them tested positive for anti-SSA/Ro and anti-SSB/La antibodies. In addition to routine fetal echocardiography, fMCG was used. Fetal cardiac time intervals (fCTIs) were extracted from the magnetic recordings by predefined procedures. ECGs in the neonates of the study group were performed within the first month after delivery. Results: The PQ segment of the fCTI was significantly prolonged in the study group (P = 0.007), representing a delay of the electrical impulse in the atrioventricular (AV) node. Other fCTIs were within normal range. None of the anti-SSA/Ro and/or anti-SSB/La fetuses progressed to a more advanced heart block during pregnancy or after birth. Conclusion: The study identified a low-risk population within antibody positive mothers, where PQ segment prolongation is associated with a lack of progression of the disease.
    Full-text · Article · Dec 2012 · Clinical and Developmental Immunology
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    • "Intravenous immunoglobulin merits evaluation as a potential prophylactic approach in mothers who have previously had an affected child [40]. However, two studies failed to demonstrate benefit in outcome from intravenous immunoglobulin [41, 42]. On the other hand, the use of hydroxychloroquine for patients with SLE has been associated with a lower rate of NLE during pregnancy [43]. "
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    ABSTRACT: Neonatal lupus erythematosus (NLE) refers to a clinical spectrum of cutaneous, cardiac, and systemic abnormalities observed in newborn infants whose mothers have autoantibodies against Ro/SSA and La/SSB. The condition is rare and usually benign and self-limited but sometimes may be associated with serious sequelae. We review the pathophysiology, clinical features, and management of infants with this condition. Neonates with NLE should be managed at a tertiary care center. Multidisciplinary team involvement may also be indicated. In mothers with anti-Ro/SSA and/or anti-La/SSB antibodies and infants with congenital heart block, the risk of recurrence in subsequent offspring is 17-25%. Therefore, careful monitoring of subsequent pregnancies with serial ultrasonography and echocardiography is essential.
    Full-text · Article · Sep 2012
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