Neonatal lupus results from the passive transfer of autoantibodies; however, this transfer is not sufficient to cause disease. This article reviews clinical presentation with a focus on autoimmune-mediated congenital heart disease. Recent data looking for additional disease mechanisms and biomarkers as well as latest information on interventions will be reviewed. Our understanding of this rare disease is often dependent on patient participation in disease registries and biorepositories. Future participation in registries including descriptive as well as biophysical data is critical to our knowledge.
This is a preview of subscription content, log in to check access.
Buy single article
Instant unlimited access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance
Litsey SE, Noonan JA, O’Connor WN, et al. Maternal connective tissue disease and congenital heart block. Demonstration of immunoglobulin in cardiac tissue. N Engl J Med. 1985;3129:98–100.
Cimaz R, Spence DL, Hornberger L, et al. Incidence and spectrum of neonatal lupus erythematosus: a prospective study of infants born to mothers with anti-Ro autoantibodies. J Pediatr. 2003;142(6):678–83. This article is a prospective study which describes the incidence and types of neonatal lupus born to mothers with anti-Ro antibodies. Most data are from registries.
Franco HL, Weston WL, Peebles C, et al. Autoantibodies directed against sicca syndrome antigens in the neonatal lupus syndrome. J Am Acad Dermatol. 1981;4(1):67–72.
Neiman AR, Lee LA, Weston WL, et al. Cutaneous manifestations of neonatal lupus without heart block: characteristics of mothers and children enrolled in a national registry. J Pediatr. 2000;137(5):674–80.
Bouderlique C, Debillon T, Mesnard B, et al. Neonatal lupus presenting as telangiectasic and atrophic lesions. Pediatrie. 1990;45(4):251–4. Article in French 2.
Guinovart RM, Vicente A, Rovira C, et al. Facial telangiectasia: an unusual manifestation of neonatal lupus erythematosus. Lupus. 2012;21(5):552–5.
Lin C, Shyur SD, Wu JY, et al.: Facial telangiectasia—an unusual complication of neonatal lupus erythematosus: report of one case. Acta Paediatr. Taiwan. 2004;45 (4):246–248.
Thornton CM, Eichenfield LF, Shinall EA, et al. Cutaneous telangiectases in neonatal lupus erythematosus. J Am Acad Dermatol. 1995;33(1):19–25.
Heelan K, Watson R, Collins SM. Neonatal lupus syndrome associated with ribonucleoprotein antibodies. Pediatr Dermatol. 2013;30(4):416–23.
Lee LA, Sokol RJ, Buyon JP. Hepatobiliary disease in neonatal lupus: prevalence and clinical characteristics in cases enrolled in a national registry. Pediatrics. 2002;109(1), E11.
Chen CC, Lin K-L, Chen CL, et al. Central nervous system manifestations of neonatal lupus: a systematic review. Lupus. 2013;22:1484–8.
Askanase AD, Izmirly PM, Katholi M, et al. Frequency of neuro-psychiatric dysfunction in anti-SSA/SSB exposed children with and without neonatal lupus. Lupus. 2010;19:300–6.
Skog A, Tingstrom J, Salomonsson S, et al. Neurodevelopment in children with and without congenital heart block born to anti-Ro/SSA-positive mothers. Acta Pediatr. 2013;102:40–6. This is the only paper that describes neurodevelopmental outcomes of children with in utero anti-Ro antibodies comparing effects of congenital heart block to those children who had healthy hearts.
Nalli C, Iodice A, Andreoli L, et al. The effects of lupus and antiphospholipid antibody syndrome on foetal outcomes. Lupus. 2014;23:507–17.
Izmirly PM, Buyon JP, Saxena A. Neonatal lupus: advances in understanding pathogenesis and identifying treatments of cardiac disease. Curr Opin Rheumatol. 2012;24:466–72.
Izmirly PM, Saxena A, Kim MY, et al. Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation. 2011;124(9):1927–35. This is an excellent description of factors both from the mother and the fetus that might alter outcomes for cardiac neonatal lupus in a heterogenous population.
Brito-Seron P, Izmirly PM, Ramos-Casals M, et al. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol. 2015;11(5):301–12.
Brucato A, Frassi M, Franceschini F, et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by couterimmunoelectrophoresis: a prospective study. Arthritis Rheum. 2001;44:1832–5.
Costedoat-Chalumeau N, Amoura Z, Lupoglazoff JM, et al. Outcome of pregnancies in patients with anti-SSA/Ro antibodies: a study of 165 pregnancies with special focus on electrocardiographic variations in the children and comparison with a control group. Arthritis Rheum. 2004;50:2187–94.
Llanos C, Izmirly PM, Katholi M, et al. Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. Arthritis Rheum. 2009;60:3091–7.
Rivera TL, Izmirly PM, Birnbaum BK, et al. Disease progression in mothers of children enrolled in the Research Registry for Neonatal Lupus. Ann Rheum Dis. 2009;68:828–35.
Clancy RM, Kapur RP, Molad Y, et al. Immunohistologic evidence supports apoptosis, IgG deposition, and novel macrophage/fibroblast crosstalk in the pathologic cascade leading to congenital heart block. Arthritis Rheum. 2004;50:173–82.
Scarsi M, Radice A, Pregnolato F, et al. Anti-Ro/SSA-p200 antibodies in the prediction of congenital heart block. An Italian multicenter cross-sectional study on behalf of the ‘Forum Interdisciplinare per la ricerca nelle Malattie Autoimmuni (FIRMA) group. Clin Exp Rheumatol. 2014;32:848–54.
Jaeggi E, Laskin C, Hamilton R, et al. The importance of the level of maternal anti-Ro/SSA antibodies as a prognostic marker of the development of cardiac neonatal lupus erythematosus a prospective study of 186 antibody-exposed fetuses and infants. J Am Coll Cardiol. 2010;55:2778–84.
Lindip R, Arentz G, Thurgood LA, et al. Pathogenicity and proteomic signatures of autoantibodies to Ro and La. Immunol Cell Biol. 2012;90:304–9.
Strandberg LS, Cui X, Rath A, et al. Congenital heart block maternal sera autoantibodies target an extracellular epitope on the alpha 1G T-type calcium channel in human fetal hearts. PLoS One. 2013;8, e72668. This paper describes the identification of a calcium channel autoantibody from maternal human serum that could account for changes in the conduction system. It has been unclear to date why anti-SSA/SSB antibodies specifically target the conduction system.
Clancy RM, Backer CB, Yi X, et al. Cytokine polymorphisms and histologic expression in autopsy studies: contribution of TNF-alpha and TGF-beta 1 to the pathogenesis of autoimmune-associated congenital heart block. J Immunol. 2003;171:3253–61.
Stevens AM, Hermes HM, Rutledge JC, et al. Myocaridal-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block. Lancet. 2003;362:1617–23.
Stevens AM, Hermes HM, Lambert NC, et al. Maternal and sibling microchimerism in twins and triplets discordant for neonatal lupus syndrome-congenital heart block. Rheumatology(Oxford). 2005;44:187–91.
Saxena A, Izmirly PM, Han SW, et al. Serum biomarkers of inflammation, fibrosis, and cardiac function in facilitating diagnosis, prognosis, and treatment of anti-SSA/Ro-associated cardiac neonatal lupus. J Am Coll Cardiol. 2015;66:930–9. This is an excellent study describing potential biomarkers that can identify and assess risk for infants exposed to anti-SSA/Ro antibodies.
Pisoni CN, Brucato A, Ruffatti A, et al. Failure of intravenous immunoglobulin to prevent congenital heart block: findings of a multicenter, prospective, observational study. Arthritis Rheum. 2010;62:1147–52.
Friedman DM, Llanos C, Izmirly PM, et al. Evaluation of fetuses in a study of intravenous immunoglobulin as a preventive therapy for congenital heart block: results of a multicenter, prospective, open-label clinical trail. Arthritis Rheum. 2010;62:1138–46.
Izmirly PM, Saxena A, Sahl S, et al. Assessment of fluorinated steroids to avert progression and mortality in anti-SSA/Ro-associated cardiac injury limited to the fetal conduction system. Ann Rheum Dis. 2015;75(6):1161–6. This study demonstrates the lack of utility of fluorinated steroid treatment as an intervention in utero for autoimmune-mediated heart block.
Jaeggi ET, Fouron JC, Silverman ED, et al. Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation. 2004;110:1542–8.
Brucato A, Ramoni V, Gerosa M et al. Congenital fetal heart block: a potential therapeutic role for intravenous immunoglobulin Obstet Gynecol 2011; 117(177).
Trucco SM, Jaeggi E, Cuneo B, et al. Use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody-mediated cardiomyopathy. J Am Coll Cardiol. 2011;57:715–23.
Cuneo BE, Lee M, Roberson D, et al. A management strategy for f or fetal immune-mediated atrioventricular block. J Matern Fetal Neonatal Med. 2010;23:1400–5. This paper describes a strategy for treating the fetus in utero including a biophysical profile and progression of intervention for heart failure and bradycardia.
Clowse ME, Madger L, Witter F, et al. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 2006;54:3640–7.
Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated with a reduce risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 2012; 126976–82. This paper describes the decreased rate of autoimmune-mediated heart block in mothers being treated with hydroxychloroquine and prompted the current interventional study of hydroxychloroquine in anti-Ro positive mothers during pregnancy.
Bergman G, Eliasson H, Mohlkert LA, et al. Progression to first-degree heart block in preschool children exposed in utero to maternal anti-SSA/’Ro52 autoantibodies. Acta Paediatr. 2012;101:488–93.
Bergman G, Skog A, Tingstrom J, et al. Late development of complete atrioventricular block may be immune mediated and congenital in origin. Acta Paediatr. 2014;103:275–81.
Skog A, Eliasson H, Tingstrom J, et al. Long term growth of children with autoantibody mediated congenital heart block. Acta Paediatr. 2013;102:718–26.
Davey DL, Bratton SL, Bradkley DJ, et al. Relation of maternal anti-Ro/La antibodies to aortic dilation in patients with congenital complete heart block. Am J Cardiol. 2011;108:561–4.
Conflict of Interest
MSKG reports grants from Alliance for Lupus Research, Lupus Foundation of America, and NIAMS, outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by the author (MSKG).
This article is part of the Topical Collection on Pediatric Rheumatology
About this article
Cite this article
Klein-Gitelman, M.S. Neonatal Lupus: What We Have Learned and Current Approaches to Care. Curr Rheumatol Rep 18, 60 (2016) doi:10.1007/s11926-016-0610-z
- Neonatal lupus
- Passive immune injury
- Autoimmune-mediated congenital heart disease
- Patient registries