Elsevier

Autoimmunity Reviews

Volume 14, Issue 12, December 2015, Pages 1154-1160
Autoimmunity Reviews

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

https://doi.org/10.1016/j.autrev.2015.08.005Get rights and content

Abstract

Background

Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB.

Methods

Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies.

Results

214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB.

In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p < 0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7–32.7]) and prematurity (p = 0.002; HR 17.1 [95%CI 2.8–103.1]).

During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p = 0.0157; HR 6.37 [95%CI: 1.25–32.44]), postnatal DCM (p < 0.0001; HR 227.58[95%CI: 24.33–2128.46]) and pacemaker implantation (p = 0.0035; HR 0.11[95%CI: 0.02–0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB.

Conclusion

In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.

Introduction

Neonatal lupus syndrome caused by passive transplacental passage of maternal anti-SSA and/or anti-SSB antibodies is a rare disorder mainly represented by cardiac neonatal lupus and skin rash. Cardiac manifestations include congenital heart block (CHB), endocardial fibroelastosis (EFE) and dilated cardiomyopathy (DCM) [1], [2], [3], [4], [5], [6], [7], [8], [9]. CHB is defined by atrio-ventricular block occurring in utero or in the neonatal period (< 28 days of life) [9]. Its prevalence is less than 1% in anti-SSA-positive women [9], [10] and the recurrence rate is estimated at 19% [11]. Its treatment is currently very controversial. Fluorinated steroids, that do cross the placenta, have been used for some decades, including in France but their efficacy has been recently challenged by 2 different groups [12], [13].

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. Buyon first established the US registry of neonatal lupus and recently reported 312 cases of second- and third-degree CHB [13]. A European and Brazilian study, which did not include French cases, reported 175 CHB cases, but only 131 with anti-SSA or anti-SSB antibodies [12]. To our knowledge, no data on other large registries are available.

Here, we give a descriptive analysis of 214 cases of high-degree CHB associated with maternal anti-SSA and/or -SSB antibodies that are included in the neonatal lupus French registry.

Section snippets

Patients

This registry, established in 2000 with Institutional Review Board approval, includes fetuses or children with neonatal lupus born to mothers with anti-SSA and/or anti-SSB antibodies. Inclusion criteria were (1) enrolment in the registry by September 2014, (2) maternal anti-SSA and/or anti-SSB antibodies, (3) confirmation of second- or third-degree CHB documented by electrocardiography and/or fetal echocardiography, and (4) diagnosis of CHB in utero or in the neonatal period. In cases of CHB

Patient demographics

By September 2014, the registry included 254 cases of cardiac neonatal lupus: 214 cases of second- or third-degree CHB, 19 cases of EFE, 13 heart blocks diagnosed after the neonatal period and 8 other miscellaneous manifestations. To have homogeneous data and according to our inclusion and exclusion criteria, we analyzed data of the 214 advanced CHB cases.

These 214 fetuses or children were born to 195 mothers between 1976 and 2014 (142 pregnancies between 2000 and 2014); 194 mothers (99.5%)

Discussion

We report for the first time, data from the French national registry of neonatal lupus syndrome, with 214 cases of high-degree CHB associated with anti-SSA and/or anti-SSB antibodies. By comparison, the two other large studies from the US registry [13] and from a European/Brazilian registry [12] recently included 278 and 131 of such cases, respectively. Maternal disease data were relatively similar between the three registries, most of the mothers having no CTD. The respective number of cases

Conclusion

We confirmed some of the previous results from other large registries. Unfortunately, our data do not support the routine use of in utero fluorinated steroids for the treatment of cardiac neonatal lupus syndrome.

Funding sources

None.

Disclosures

None.

Take-home messages

  • Feto-neonatal mortality of CHB was 15.7%.

  • Factors associated with feto-neonatal deaths were hydrops and prematurity.

  • During a median follow-up period of 7 years [birth to 36 years] of 148 children born alive, 79% had a pacemaker, 19% had DCM, and 12% died.

  • Factors associated with child death were in utero DCM, postnatal DCM and pacemaker implantation.

  • We found no evidence that the use of fluorinated steroids was associated with improved survival or with regression of 2nd degree CHB.

Acknowledgments

We acknowledge the doctors participating to the “Neonatal Lupus Group”, the “Société Nationale Française de Médecine Interne” and the families for their kind collaboration.

This study is dedicated to recently deceased Professor Olivier Meyer.

References (25)

  • L.E. Nield et al.

    Maternal anti-Ro and anti-La antibody-associated endocardial fibroelastosis

    Circulation

    (2002)
  • P. Brito-Zeron et al.

    The clinical spectrum of autoimmune congenital heart block

    Nat Rev Rheumatol

    (2015)
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    1

    These 3 authors contributed equally to this work.

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