Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern, 2012, Annals of the Rheumatic Diseases, (71) Methods. The influence of fetal gender, maternal age, parity and time of birth on heart block development was analyzed in 145 families including Ro/La-positive (n= 190) and Ro/Lanegative (n=165) pregnancies.Results. We observed a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was however significantly higher than in pregnancies resulting in babies without heart block (p<0.01). Further, seasonal timing of pregnancy influenced the outcome. Gestational susceptibility-weeks 18-24 occurring during January-March correlated with a higher proportion of heart block pregnancies and lower vitamin D levels, and a corresponding higher proportion of children with heart block born in the summer (p<0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies.Conclusion. This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for congenital heart block development in Ro/La positive pregnancy. These observations indicate that the risk can be modified, and will be important for counseling when a pregnancy is considered. 4Congenital complete heart block without cardiac malformation is a rare disease, affecting 1 in 15,000 to 20,000 births in the general population. An association with the presence of maternal autoantibodies to Ro/SSA and/or La/SSB is however well established [1,2], and the risk of complete congenital heart block is 1-2% in Ro/SSA-positive pregnancies [3][4][5][6]. Furthermore, the reported risk of giving birth to a second child with complete heart block for anti-Ro/SSA positive mothers ranges from 12 to 20% [7][8][9], despite the persistence of the maternal autoantibodies [10].This indicates that additional factors are critical for establishing the heart block. Fetal genetic susceptibility has been suggested as a potential risk factor [11,12], and polymorphisms in the gene encoding TGFβ have been implicated in the development of heart block [13,14]. Variations in the intrauterine environment between pregnancies have also been suggested to contribute to the penetrance of the disease. Maternal disease severity has been investigated as such a potential risk factor, but was not found to contribute to the development of congenital heart block [15].Given the rarity of congenital heart block occurrence in the general population, it is difficult to investigate potential risk factors associated with the disease. In particular, very little information is available on the influence of maternal age and parity on pregnancy outcome in anti-Ro/La positive mothers. In an effort to address these questions in a reasonable cohort we identified heart ...

This study of CHB provides new information on the incidence of CHB and outcome of pregnancy in anti-Ro/SSA-positive women, which has clinical relevance when counseling rheumatic patients considering pregnancy.

This report documents that newborns with autoantibody-mediated second-degree or third-degree atrioventricular block are retarded in growth, with no catch-up during infancy, whereas fetuses with first-degree atrioventricular block or normal atrioventricular conduction have a normal growth soon after birth. Increased maternal age and/or parity seem to carry an increased risk for fetal heart block.

ObjectiveCongenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect for large groups of patients. We therefore used nation-wide healthcare registers to investigate comorbidity and outcomes in patients with CHB and their siblings.MethodsData from patients with CHB (n= 119) and their siblings (n= 128), all born to anti-Ro/SSA-positive mothers, and from matched healthy controls (n= 1,190) and their siblings (n= 1,071), were retrieved from the Swedish National Patient Register. Analyses were performed by Cox proportional hazard modelling.ResultsIndividuals with CHB had a significantly increased risk of cardiovascular comorbidity, with cardiomyopathy and/or heart failure observed in 20 (16.8%) patients versus 3 (0.3%) controls, yielding a HR of 70.0 (95% CI 20.8 to 235.4), and with a HR for cerebral infarction of 39.9 (95% CI 4.5 to 357.3). Patients with CHB also had a higher risk of infections. Pacemaker treatment was associated with a decreased risk of cerebral infarction but increased risks of cardiomyopathy/heart failure and infection. The risk of systemic connective tissue disorder was also increased in patients with CHB (HR 11.8, 95% CI 4.0 to 11.8), and both patients with CHB and their siblings had an increased risk to develop any of 15 common autoimmune conditions (HR 5.7, 95% CI 2.83 to 11.69 and 3.6, 95% CI 1.7 to 8.0, respectively).ConclusionsThe data indicate an increased risk of several cardiovascular, infectious and autoimmune diseases in patients with CHB, with the latter risk shared by their siblings.

Neonatal lupus erythematosus (NLE) develops in foetuses of mothers with Ro/SSA and La/SSB antibodies and may include foetal atrioventricular block and dermatologic manifestations. In this study, we investigated postnatal Ro and La IgG, IgA and IgM antibody levels up to 1 year of age in 32 children born to Ro/SSA positive mothers. Antibody levels were correlated with NLE manifestations, and the role of breast feeding in transfer of autoantibodies from mother to child was evaluated. Ro52, Ro60 and La IgG antibodies all transferred from the mothers to their foetus in utero and were present in the infant at birth as detected by enzyme-linked immunosorbent assay using recombinant antigens and a synthetic peptide. A significant decrease in Ro52, Ro60 and La IgG autoantibody levels of the infants was observed from birth to 4-5 weeks of age (P < 0.05, P < 0.05 and P < 0.01). Ro- and La-specific IgA and IgM antibodies were detected in the serum from a subset of mothers. However, Ro- and La-specific IgA and IgM antibody levels were low or non-detectable in children raised both with and without breastfeeding. Furthermore, NLE skin lesions developed independently of breastfeeding. Our findings support a role for placental materno-foetal transfer of IgG autoantibodies in the pathogenesis of NLE and indicate that refraining from breastfeeding does not protect from NLE skin involvement.