Background Several studies have evaluated mortality and short term morbidity in neonatal lupus (NL), however there is minimal data on long term outcomes in children exposed to maternal anti-Ro antibodies in utero. A previous pilot study utilising the Research Registry for Neonatal Lupus (RRNL) raised concern regarding the development of autoimmune disease in childhood, however the numbers evaluated were small and the patients studied were young. This study was initiated to ascertain the current prevalence of autoimmune disease in NL children and their unaffected siblings, and to evaluate whether fetal or maternal factors associated with the development of future autoimmunity.

Materials and methods A retrospective cohort of family members from the RRNL were contacted to evaluate for autoimmune disease. Follow-up questionnaires were completed which included 35 items describing symptoms and diagnoses associated with autoimmunity in 138 cardiac NL children, 74 cutaneous NL children, and 134 unaffected siblings. Medical records were obtained and evaluated from the patient’s physicians to confirm diagnoses. Maternal diagnosis of systemic lupus and/or Sjogren’s syndrome and fetal cardiac disease severity based on a previously described severity score were associated with postnatal autoimmune diseases using chi square and Mann-Whitney analyses.

Results Seventeen (8.0%) of NL affected children developed an autoimmune disease at the time of follow up (mean age 11.6±9.0 years). These included 3 patients with SLE, 1 with JIA, 3 with thyroid disease, 5 with psoriasis, 1 with IBD, 1 with uveitis, 1 with UAS and 2 with type 1 DM. Six (4.5%) unaffected siblings developed an autoimmune disease (mean age 10.6±7.1 years), which included 1 with JIA, 1 with Sarcoidosis/ITP, 1 with Myasthenia Gravis/Celiac disease, 1 with psoriasis, 1 with UAS and 1?with type 1 DM,. There was a significant association of between having an autoimmune disease and having advanced heart block (11.0% vs. 4.2%, p = 0.03) and a trend towards an association with cardiac NL disease severity score (4.43±4.89 vs. 2.58±4.24, p = 0.06). Mother’s diagnosis of SLE or Sjogren’s did not associate with the children’s development of autoimmune disease (p = 0.828).

Conclusions Fetuses that develop advanced congenital heart block as a manifestation of NL may be at greater risk for developing autoimmune diseases later in life. This could potentially relate to a genetic component that makes a Ro exposed fetus both more prone to inflammatory effects of passive immunity and predisposes to future autoimmunity, independent of the mother’s rheumatic disease status.