Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern

Abstract

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 ...

A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus

“…Cardiac NL is less common than other NL manifestation and the risk of CHB is higher in anti-Ro/SSA positive women with pSS or other autoimmune diseases, than in women with SLE [11,89]. The incidence of cardiac NL manifestations increases in women with anti-Ro/SSA and/or anti-La/SSB antibodies who have had a previous child with CHB, being the recurrence estimated between 12% [90] and 17% [91]. The risk of cardiac-NL is similarly elevated in the offspring of women with anti-Ro/SSA and/ or anti-La/SSB antibodies who had a previous child with cutaneous NL without cardiac manifestations [92].…”

Pregnancy implications for systemic lupus erythematosus and the antiphospholipid syndrome

“…Cardiac NL is less common than other NL manifestations, affecting approximately 2% of exposed offspring [32]. However, the recurrence of cardiac NL is much more frequent in subsequent pregnancies, being estimated between 12% [33] and 17% [34]. Cutaneous NL can be also a predictor of cardiac NL (6e10 fold risk of a subsequent child developing cardiac NL) [35].…”

“…However, some studies were able to identify non-genetic maternal factors as predictors of CHB. Older maternal age and birth during summertime were found to be associated with the development of CHB [33]. Exposure to HCQ during pregnancy in mothers with SLE and anti-Ro/SSA and anti-La/SSB antibodies was reported to decrease the risk of foetal development of cardiac NL [41].…”

Neonatal Lupus

“…The study authors posited that a decrease in sun exposure and vitamin D levels during the winter months in Sweden may explain this phenomenon. The average vitamin D level in each month, calculated based on samples from healthy Swedish woman, was inversely correlated with the number of heart block pregnancies in autoantibody positive women [ 85 ]. The authors acknowledged that other winter-related events such as viral infections might also contribute to the above observation [ 85 ].…”

“…A recent study in a Swedish population-based cohort of 190 pregnancies identifi ed maternal age and seasonal timing of pregnancy as being novel risk factors for CHB in mothers with anti-SSA/Ro and/or anti-SSB/La antibodies [ 85 ]. Older maternal age (29.5 vs. 26.6) was signifi cantly associated with cardiac-NL.…”