Autoimmune congenital heart block

Version: 3.2
Published: 15 April 2025
Condition for which Ig use is in exceptional circumstances only

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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
  • Postnatal 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 the predetermined stopping rule of three affected cases was 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
Postnatal treatment of congenital heart block where SSB (La) and/or SSA (Ro) are present
This indication relates only to treatment of congenital heart block where SSB (La) and/or SSA (Ro) are present in patients up to 6 months of age. Pregnant women are eligible under the indications prevention of recurrent autoimmune congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are present or maternal therapy for treatment of congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are identified.
  • 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
Postnatal treatment of congenital heart block where SSB (La) and/or SSA (Ro) are present

This indication relates only to treatment of congenital heart block where SSB (La) and/or SSA (Ro) are present in patients up to 6 months of age. Pregnant women are eligible under the indications prevention of recurrent autoimmune congenital heart block where maternal SSB (La) and/or SSA (Ro) antibodies are present or 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 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.
 Dose Calculator
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.
 Dose Calculator
Postnatal 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.
 Dose Calculator
Bibliography

Buyon JP, Kim MY, Copel JA et al (2001) ‘Anti-Ro/SSA antibodies and congenital heart block: necessary but not sufficient’, Arthritis & Rheumatism, 44(8):1723–7, https://doi.org/10.1002/1529-0131(200108)44:8%3C1723::aid-art305%3E3.0.co;2-0.  

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, 62(4):1138–1146, https://doi.org/10.1002/art.27308.  

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, 48(1):280–1, https://doi.org/10.1002/art.10716.

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, 21(6):666 –71, https://doi.org/10.1177/0961203311430969.

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, 34(4):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, 22(6):263–7, https://doi.org/10.1097/crd.0000000000000026. 

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, 35(11):1148–1150, https://doi.org/10.1002/pd.4651. 

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, 50(1):337–8, https://doi.org/10.1002/art.11498.

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, 48(8):1682–7, https://doi.org/10.1016/j.jacc.2006.07.034. 

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, 41(3):339–41, https://doi.org/10.1111/j.1479-828x.2001.tb01243.x.