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Background/Purpose: It had been suggested that prenatal exposure to hydroxychloroquine reduced the risk of cardiac NLE. The primary aim was to assess if prenatal exposure to antimalarials (AM) decreased the risk of cardiac NLE. The secondary aim was to analyze the effect of AM exposure on the risk of non-cardiac NLE. Methods: A retrospective cohort study was performed on a large single-center cohort of children exposed to anti-Ro and/or anti-La antibodies on whom prospective data has been collected since 1984. Inclusion criteria were: 1) first child born from a woman positive for anti-Ro and/or anti-La antibodies with a diagnosis of cutaneous lupus, systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis or rheumatoid arthritis, 2) the mother underwent fetal chocardiography screening during pregnancy and/or the child had a postnatal ECG and 3) the child was ≥6 months old as of October 2013. We used Bayesian analysis for the association between prenatal use of AM and NLE. Results: The study population consisted of 265 children, of whom 72 were exposed to AM throughout gestation. Full laboratory data was available on 216 infants: 101 (46.8%) developed NLE and 115 (53.2%) remained unaffected. Forty nine children were classified as having no cardiac NLE but could not be diagnosed as true unaffected children as one or more blood test components were missing. These children were only included when the outcome studied was cardiac NLE. On univariable analysis and under a non-informative prior, the probability that prenatal AM exposure would be protective (RR < 1) was 97.1% for cardiac and 66.9% for non-cardiac NLE. On multivariable analysis, the RRs obtained were numerically higher, but still suggestive of a protective effect (). Using a more stringent RR cutoff (RR < 0.75), the effect on the outcome cardiac NLE remained significant, unlike for non-cardiac NLE for which probabilities dropped significantly. [ABSTRACT FROM AUTHOR]

Background/Purpose: Little is known about the long-term morbidity and mortality of childhood-onset SLE (cSLE) after transition to adult care; however, linking clinical data to administrative databases enables study of previously unknown outcomes. Our objectives were to describe long-term outcomes in young adults with cSLE, including: i) cardiovascular outcomes; ii) renal outcomes; iii) joint replacement surgery due to avascular necrosis; iv) malignancies; and v) pregnancies and births. Methods: A retrospective chart review of all cSLE patients (<18 years at diagnosis) diagnosed between Jan 1, 1984 and Dec 31, 2011 and followed for ≥1 year was conducted after contacting all pediatric and adult rheumatologists and nephrologists practicing in Ontario. Clinical data and Ontario Health Insurance Plan (OHIP) numbers were securely transferred to the Institute for Clinical Evaluative Sciences (ICES). OHIP numbers were transformed into an encrypted ICES key number (IKN) used to link the cohort to multiple administrative datasets to determine the outcomes of interest. Outcomes were determined using validated definitions. Means ± standard deviations are given unless noted. Results: 622 cSLE patients are included in this inception cohort. The cohort was predominantly female (81%) with mean follow-up of 10.7 ± 7.3 years, representing 6629 person-years of disease. Age at diagnosis was 12.8 ± 3.2 years. There were 34 (6%) hospitalizations for cerebrovascular events, at mean age 18.1 ± 7.7 years, and disease duration 6.7 ± 7.0 years. Fewer than 6 hospitalizations for myocardial infarctions occurred at a median disease duration of 10.7 years. 273 (44%) patients had biopsy-proven lupus nephritis, with end stage renal disease occurring in 20 (7.3%) of these patients at mean age 31.4 ± 8.0 years, and disease duration 17.5 ± 8.7 years. Eight patients underwent renal transplant. Twenty-two (3.5%) patients have had 32 hip replacement surgeries, at mean age 24.2 ± 6.6 years and disease duration 10.1 ± 6.7 years. Fewer than 6 patients have had knee and/or ankle replacement surgery. Fourteen malignancies occurred in 13 (2%) patients, at mean age 28.2 ± 9.2 years and disease duration 16.5 ± 7.2 years. Nine were female reproductive and/or hematologic malignancies. Obstetrical outcomes were examined in females ages 15-45 years. Of 222 pregnancies, there were 82 (37%) live births, occurring at mean age 26.4 ± 4.9 years and disease duration 12.1 ± 5.5 years. Fewer than 6 pregnancies resulted in twins. There were 90 (41%) therapeutic abortions, 39 (18%) miscarriages, and 8 (4%) still births. Conclusion: Myocardial infarction and end-stage renal failure rates in this cohort with universal healthcare appear to be lower than reported in other populations. Cerebrovascular disease, hip replacement surgery and malignancies were significant morbidities in this cohort of young adults. Many women were able to conceive and deliver live infants; however, the miscarriage and stillbirth rates were greater than expected for young women. [ABSTRACT FROM AUTHOR]

Background/Purpose: Neonatal lupus erythematosus (NLE) is a passively transferred autoimmune disease that occurs in babies born to mothers with anti-Ro and anti-La antibodies. The most serious complication of NLE is congenital heart block (CHB). In pregnancies of mothers with a known autoimmune condition and positive anti-Ro antibodies, the incidence of heart block is approximately 1-2% of live births. We have previously shown that only mothers with moderate-high titre antibodies are at risk to deliver a child with CHB. However, the rate of anti-Ro positive antibody pregnant women in an otherwise healthy population is unknown or is their risk for delivering a child with CHB. Objectives: Determine the rate of anti-Ro/La antibodies in the general pregnant population., Determine if the incidence of CHB is increased in healthy mothers with positive Ro/La antibodies compared to mothers with known autoimmune disease and positive anti-Ro/La antibodies., Methods: Antibody testing was performed on 15198 pregnant women who were having concurrent Maternal Serum Screening in the Metropolitan Toronto area. Maternal self-reported outcomes of prenatal, pregnancy, and post-natal medical conditions were reported, along with fetal outcomes of pre and post-natal illnesses. Autoantibody titres were stratified into negative, low, moderate, and high positive. Results: 1152/151598 (7.6%) of the mothers who had anti-Ro antibodies and 179/15198 (1.18%) had moderate-high titres (at risk to deliver a child with CHB). 779 (5%) had anti-La antibodies with the majority being low titre. During the course of the study there were 13 cases of CHB that were unrelated to our maternal sample population- 10 to well mothers and 3 to mothers with an autoimmune disease. All of these women mothers had moderate-high titre anti-Ro antibodies, while only 31% had moderate-high titre anti-La antibodies. During the course of the study 64 pregnant women with a known autoimmune disease and anti-Ro antibodies (at risk to deliver a child with CHB) were prospectively followed. 3/64 delivered a child with CHB. All 3 of these mothers had moderate-high titre anti-Ro antibodies while 41/61 mothers who delivered a child without CHB had moderate-high titre anti-Ro antibodies. Therefore 3/44 (6.9%) mothers with moderate-high titre anti-Ro antibodies and an autoimmune disease delivered a child with CHB. Conclusion: The incidence of CHB is reported to be between 1:10/N15,000 pregnancies. Therefore, based on our data showing 1.18% of otherwise well pregnant woman had moderate-high titre anti-Ro antibodies (at risk to deliver a child with CHB), for each child with CHB we predict that 117-174 children without CHB will be delivered to otherwise healthy mothers. In contrast, in mothers with a known autoimmune disease and moderate-high anti-Ro antibody titre, we found a 6.9% incidence of CHB and therefore for each child with CHB there were 14 children without CHB born. Therefore the risk for a woman with a known autoimmune disease and moderate-high titre anti-Ro antibodies was approximately 10x that of otherwise healthy pregnant women. These data therefore suggest that the anti-Ro antibody repertoire differs between these 2 groups of pregnant women. [ABSTRACT FROM AUTHOR]