Type I IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero.

OBJECTIVE: In utero exposure of the fetus to Ro/La autoantibodies may lead to congenital heart block (CHB). In the mother, these autoantibodies are associated with activation of the type I interferon (IFN)-system. As maternal autoantibodies are transferred to the fetus during pregnancy, we investigated whether the type I IFN-system is activated also in newborns of anti-Ro/La positive mothers, and whether fetal IFN activation is affected by maternal immunomodulatory treatment. METHODS: Blood drawn at birth from anti-Ro/La positive mothers, their newborns and healthy control pairs was separated into plasma and peripheral blood mononuclear cells (PBMC). PBMC were analysed directly or cultured. mRNA expression was analysed by microarrays, cell surface markers by flow cytometry, and IFNα levels by immunoassays. RESULTS: We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/La positive women, but also in their newborns. CD14+ monocytes of both anti-Ro/La positive mothers and their neonates showed increased expression of Sialic acid-binding Ig-like lectin-1, indicating cellular activation. Notably, the IFN score of neonates born to mothers receiving immunomodulatory treatment was similar to that of controls, despite persistent IFN activation in the mothers. In both maternal and neonatal PBMC, IFNα production was induced when cells were cultured with anti-Ro/La positive plasma. CONCLUSIONS: Ro/La autoantibody-exposed neonates at risk of CHB have signs of an activated immune system with an IFN signature. This study further demonstrates that neonatal cells can produce IFNα when exposed to autoantibody-containing plasma, and that maternal immunomodulatory treatment may diminish the expression of IFN-regulated genes in the fetus.

Outcome in 212 anti-Ro/SSA-positive pregnancies and population-based incidence of congenital heart block.

INTRODUCTION: We investigated the effects of maternal autoimmune disease and fetal congenital heart block (CHB) on pregnancy outcomes in anti-Ro/SSA-positive women and assessed the population-based incidence of isolated CHB. MATERIAL AND METHODS: One hundred and ninety nine anti-Ro/SSA-positive pregnancies were prospectively followed at our center (2000-2013). Seven fetuses developed atrioventricular block (AVB) II-III. In this period, another 13 anti-Ro/SSA-positive pregnancies were referred for fetal bradycardia, subsequently diagnosed with AVB II-III. Cesarean section rates, gestational age, body measurements at birth, and the incidence of CHB in these 212 pregnancies were analyzed in relation to fetal atrioventricular conduction and maternal diagnosis and compared with data from the Medical Birth Registry on 352,104 pregnancies in the Stockholm County. RESULTS: The prevalence of maternal systemic lupus erythematosus (SLE) and primary Sjögren's syndrome and the outcomes at birth were similar in normal conduction and AVB I cases. Only 1/20 AVB II-III cases (0/7 in the surveillance group) had a mother diagnosed with SLE, compared with 73/192 in cases with normal conduction or AVB I. Excluding cases with AVB II-III, SLE mothers more frequently delivered by cesarean section (31% vs. 20%, p < 0.05) and had a higher incidence of preterm birth (13% vs. 5.8%, p < 0.05) than the county population. Both SLE and primary Sjögren's syndrome mothers had a fourfold greater rate of growth-retarded babies (10.11% vs. 2.2%, p < 0.001). The incidence of autoantibody-related AVB II-III in Stockholm County was 1/23 300. CONCLUSION: 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.

Foetal tachyarrhythmia treatment remains challenging even if the vast majority of cases have a favourable outcome.

AIM: The optimal treatment for foetal tachyarrhythmia remains controversial, and this study aimed to fill this gap in the knowledge. METHODS: We retrospectively reviewed all cases of foetal tachyarrhythmia diagnosed at two tertiary foetal cardiology centres in Sweden from 1990 to 2012. RESULTS: Of the 153 cases, 28% had atrial flutter (AF), 63% had atrioventricular reentrant tachycardia (AVRT) and 9% had other mechanisms. Hydrops was present in 45, less frequently in AF than in AVRT. Transplacental treatment was commenced in 99 and the rhythm normalised in two-thirds, without any significant difference in cardioversion rates between AF and AVRT cases or nonhydropic and hydropic foetuses. Sotalol treatment had a higher cardioversion rate than digoxin in AVRT (63% versus 33%, p < 0.05) but not in AF (57% versus 56%). Two or more drugs were used in 38%. Neonatal survival was 100% in nonhydropic and 84% in hydropic cases. After a median of eight years, 11/134 patients still had arrhythmias, one had died due to arrhythmia and another had undergone cardiac transplantation. CONCLUSION: Transplacental treatment was frequently insufficient to obtain cardioversion in nonhydropic and hydropic foetuses, but all nonhydropic cases had favourable outcomes. Larger prospective studies are needed to optimise the treatment of cases with hydrops.