Autoimmune congenital heart block

Version: 3.1
Published: 20 March 2020
Condition for which Ig use is in exceptional circumstances only

This medical condition has either been superseded or has become inactive
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Specific Conditions
  • Risk of autoimmune congenital heart block – previously affected sibling
  • Confirmed autoimmune congenital heart block in a fetus
  • Confirmed autoimmune congenital heart block in a neonate
Indication for Ig Use
  • Prevention of recurrent autoimmune congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are present
  • Maternal therapy for treatment of congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are identified
  • Post-natal treatment of congenital heart block where SSB (La) and/or SSA (Ro) are present
Level of Evidence Insufficient data (Category 4a)
Description and Diagnostic Criteria Congenital heart block (CHB), the most serious manifestation of neonatal lupus erythematosus, is an autoantibody mediated disorder potentially caused by placental transmission of maternal autoantibodies to 52-kd and 60-kd SSA/Ro +/-48-kd SSB/La ribonucleo- proteins. These antibodies can cause permanent and often life- threatening damage to the fetal heart. The incidence of CHB in the offspring of mothers with pathologic autoantibodies is one to two percent but the recurrence rate in subsequent pregnancies following the birth of a child with neonatal lupus is 18 percent.
Justification for Evidence Category Multiple positive case reports and case series preceded and followed the report of a multicenter open-label study (Friedman et al, 2010). Enrollment criteria included: maternal anti-SSA/Ro antibody, a previous child with CHB/rash, </= 20 mg prednisone, less than 12 weeks pregnant. IVIG (400mg/kg) was given every three weeks from 12 to 24 weeks of gestation. Study prematurely ceased after 20 patients because stopping rule of three affected cases reached. However, majority of successful reports used higher doses +/- frequency of IVIG (1-2g/kg 2 to 4 weekly) which are more likely to be immunomodulatory, often throughout the pregnancy and sometimes, when evidence of early disease, extending to the newborn until disappearance of maternal antibodies.
 
A combination treatment of steroids, plasmapheresis and IVIg until delivery followed by IVIg in the infant until disappearance of maternal antibodies resulted in reversal of the severity of heart block detected in the infants of two women without previous affected infants.
 
The general conclusion is that it is well tolerated and although replacement dose IVIg does not prevent CHB, high dose IVIg is effective in some patients.  
Diagnosis Requirements

A diagnosis must be made by an Immunologist, Maternal-Fetal Medicine Specialist or an Obstetrician.
Qualifying Criteria for Ig Therapy
Prevention of recurrent autoimmune congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are present
  • Current pregnancy with a history of autoimmune congenital heart block in at least one previous pregnancy
     
  • AND
  • Maternal SSB (La)-and/or SSA (Ro)-antibodies are present
     
Maternal therapy for treatment of congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are identified
  • Current pregnancy and evidence of congenital heart block
     
  • AND
  • Maternal SSA (Ro) and/or SSB (La) antibodies are identified
     
AND
  • Ig therapy will be given concurrently with steroid therapy with or without plasmapheresis
  • OR
  • Steroid treatment is contraindicated or has resulted in unacceptable side effects or significant toxicity
     
Post-natal treatment of congenital heart block where SSB (La) and/or SSA (Ro) are present
  • Neonate with congenital heart block
     
  • AND
  • SSB (La) and/or SSA (Ro) antibodies are present in the neonate
     
Review Criteria for Assessing the Effectiveness of Ig Use
Prevention of recurrent autoimmune congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are present
Review is not mandated for this indication however the following criteria may be useful in assessing the effectiveness of Ig therapy.
 
  • Absence of symptoms of CHB in fetus and/or live birth of healthy neonate
     
  • AND
  • Reduction in the level or absence of maternal SSA (Ro) and/or SSB (La) antibodies
     
Maternal therapy for treatment of congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are identified
Review is not mandated for this indication however the following criteria may be useful in assessing the effectiveness of Ig therapy.
 
  • Congenital heart block has improved in response to Ig therapy
     
  • AND
  • Reduction in the level or absence of maternal SSB (La) and/or SSA (Ro) antibodies
     
Post-natal treatment of congenital heart block where SSB (La) and/or SSA (Ro) are present
Review is not mandated for this indication however the following criteria may be useful in assessing the effectiveness of Ig therapy.
 
  • Congenital heart block has improved in response to Ig therapy
     
  • AND
  • Reduction in the level or absence of SSA and/or SSB antibodies
     
Dose
Prevention of recurrent autoimmune congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are present
  • Induction Dose (IVIg) - Up to 2g/kg in a single or divided dose. This may be given as two doses of 1g/kg at fortnightly intervals.
  • Maintenance Dose (IVIg) - 1-2g/kg monthly in single or divided doses. A maximum dose of 2g/kg may be given in any four week period. This might be by divided doses more frequently than monthly.
Refer to the current product information sheet for further information on dose, administration and contraindications.
Maternal therapy for treatment of congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are identified
  • Induction Dose (IVIg) - Up to 2g/kg in a single or divided dose. This may be given as two doses of 1g/kg at fortnightly intervals.
  • Maintenance Dose (IVIg) - 1-2g/kg monthly in single or divided doses. A maximum dose of 2g/kg may be given in any four week period. This might be by divided doses more frequently than monthly.
Refer to the current product information sheet for further information on dose, administration and contraindications.
Post-natal treatment of congenital heart block where SSB (La) and/or SSA (Ro) are present
  • Induction Dose (IVIg) - Up to 2g/kg in a single or divided dose. This may be given as two doses of 1g/kg at fortnightly intervals.
  • Maintenance Dose (IVIg) - 1-2g/kg monthly in single or divided doses. A maximum dose of 2g/kg may be given in any four week period. This might be by divided doses more frequently than monthly.
Refer to the current product information sheet for further information on dose, administration and contraindications.
Bibliography
Buyon, JP, Kim, MY, Copel, JA, et al 2001, ‘Anti-Ro/SSA antibodies and congenital heart block: necessary but not sufficient’, Arthritis & Rheumatism, vol. 44, no. 8, pp. 1723–7. https://www.ncbi.nlm.nih.gov/pubmed/11508420

Friedman, DM, Llanos, C, Izmirly, PM, et al 2010, ‘Evaluation of Fetuses in the Preventive IVIG Therapy for Congenital Heart Block (PITCH) study’, Arthritis Rheumatism, vol. 62, no. 4, pp. 1138–1146. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214993/

Kaaja, R & Julkunen, H 2003, ‘Prevention of recurrence of congenital heart block with intravenous immunoglobulin and corticosteroid therapy: comment on the editorial by Buyon et al’, Arthritis & Rheumatism, vol. 48, no. 1, pp. 281–2. https://www.ncbi.nlm.nih.gov/pubmed/12528144

Ruffatti, A, Milanesi, O, Chiandetti, L, et al 2012, ‘A combination therapy to treat second-degree anti-Ro/La-related congenital heart block: a strategy to avoid stable third-degree heart block?’, Lupus, vol. 21, no. 6, pp. 666 –71. https://www.ncbi.nlm.nih.gov/pubmed/22187163

Ruffatti, A, Cerutti, A, Favaro, M, et al 2016, ‘Plasmapheresis, intravenous immunoglobulins and bethametasone - a combined protocol to treat autoimmune congenital heart block: a prospective cohort study’, Clinical & Experimental Rheumatology, vol. 34, no. 4, pp. 706-13. https://www.ncbi.nlm.nih.gov/pubmed/27385463

Saxena, A, Izmirly, PM, Mendez, B, et al 2014, ‘Prevention and Treatment In Utero of Autoimmune-Associated Congenital Heart Block’, Cardiology in Review, vol. 22, no. 6, pp. 263–7. https://www.ncbi.nlm.nih.gov/pubmed/25050975

Sterling, R-A & Carlin, A 2015, ‘Prevention of recurrent congenital heart block in a SSA/SSB positive mother using high dose maternal IVIG from 16-week gestation’, Obstertrics & Gynaecology, vol. 35 issue 11, pp.1148–1150. http://onlinelibrary.wiley.com/doi/10.1002/pd.4651/abstract

Tran, HB, Cavill, D, Buyon, JP, et al 2004, ‘Intravenous immunoglobulin and placental transport of anti-Ro/La antibodies: comment on the letter by Kaaja and Julkunen’, Arthritis & Rheumatism, vol. 50, no. 1, pp. 337–8. https://www.ncbi.nlm.nih.gov/pubmed/14730639

Villain, E, Coastedoat-Chalumeau, N, Marijon, E, et al 2006, ‘Presentation and prognosis of complete atrioventricular block in childhood, according to maternal antibody status’, Journal of the American College of Cardiology, vol. 48, no. 8, pp. 1682–7. https://www.ncbi.nlm.nih.gov/pubmed/17045907

Wong, JP, Kwek, KY, Tan, JY, et al 2001, ‘Fetal congenital complete heart block: prophylaxis with intravenous gammaglobulin and treatment with dexamethasone’, Australia New Zealand Journal of Obstetrics and Gynaecology, vol. 41, no. 3, pp. 339–41. https://www.ncbi.nlm.nih.gov/pubmed/11592556