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Objective: Our objective was to evaluate the development of a systemic autoimmune rheumatic disease (SARD) in undifferentiated and asymptomatic individuals with antinuclear antibodies (ANAs). We comparatively evaluated those who did and did not develop a SARD and fulfillment of classification criteria. Methods: We conducted a cohort study of undifferentiated and asymptomatic patients with ANAs who were assessed for the development of a SARD. The primary outcome was a diagnosis of a SARD over a two‐year period. We assessed fulfillment of classification criteria. Risk ratios (RRs) were used to evaluate differences among those who did and did not progress to a SARD. Results: We evaluated 207 asymptomatic ANA‐positive or undifferentiated patients, of whom 23 (11%) progressed to a SARD, whereas 187 (89%) did not progress. Progressors developed systemic lupus erythematosus (SLE) (n = 11 [48%]), Sjögren disease (n = 5 [22%]), systemic sclerosis (n = 3 [13%]), rheumatoid arthritis (n = 1 [4%]), and from ANA‐positive to undifferentiated connective tissue disease (n = 3 [13%]). Fever (RR 0.89, 95% confidence interval [CI] 0.8–0.93) and antiphospholipid antibodies (RR 0.89, 95% CI 0.87–0.93) occurred less frequently, whereas arthritis (RR 1.74, 95% CI 1.20–2.55) occurred more frequently in progressors. Progressors to SLE had arthritis (91%), whereas none developed delirium, psychosis, or nephritis. Among patients with SLE, 100% fulfilled the EULAR/American College of Rheumatology (ACR) SLE criteria (sensitivity 91.7%, specificity 100%), whereas 73% fulfilled the 1997 ACR SLE criteria (sensitivity 81.8%, specificity 98.9%). Conclusion: Most undifferentiated/asymptomatic individuals with ANA do not progress to a SARD over a two‐year period. SLE progressors appear to have mild disease in the short term. The EULAR/ACR SLE criteria have improved ability to identify those who develop SLE. [ABSTRACT FROM AUTHOR]

Objective: Anti‐Ro antibody–positive mothers are frequently referred for serial echocardiography due to the fetal risk of developing heart block and endocardial fibroelastosis. Little is known why only some and not all offspring develop these cardiac manifestations of neonatal lupus (CNL). This prospective study examined associations between anti‐Ro antibody titers and fetal CNL. Methods: Antibody‐positive mothers referred since 2018 for fetal echocardiography at risk of CNL (group 1; n = 240) or with CNL (group 2; n = 18) were included. Maternal antibody titers were measured with a chemiluminescent immunoassay (CIA). Additional testing on diluted serum samples was used to quantify anti–Ro 60 antibody titers above the analytical measuring range (AMR) of the standard CIA (≥1,375 chemiluminescent units [CU]). Results: Among 27 total mothers with a fetal diagnosis of CNL, all displayed anti–Ro 60 antibody titers that exceeded the AMR of the CIA at least 10‐fold. Of 122 mothers in group 1 who underwent additional anti–Ro 60 antibody testing, event rates of CNL (n = 9) were 0% (0 of 45) among mothers with anti–Ro 60 antibody titers from 1,375–10,000 CU, 5% (3 of 56) among mothers with titers from 10,000–50,000 CU, but 29% (6 of 21) among mothers with titers >50,000 CU (odds ratio 13.1, P = 0.0008). Of mothers in group 2 with a primary diagnosis of CNL, 0% (0 of 18 mothers) had anti–Ro 60 antibody titers <10,000 CU, 44% (8 of 18 mothers) had titers from 10,000–50,000 CU, and 56% (10 of 18 mothers) had titers >50,000 CU. Conclusion: CNL is associated with substantially higher anti‐Ro antibody titers than are obtained using a standard CIA. Enhancing the assay measuring range allows an improved specificity of identifying pregnancies at risk of CNL. [ABSTRACT FROM AUTHOR]

Objective Childhood-onset SLE (cSLE) manifests differently than adult-onset SLE (aSLE). This study determined whether ethnic differences contribute to the differences in clinical presentation between the two groups. Methods This cross-sectional study used data from a multi-centred registry from eight adult and four paediatric Canadian centres gathered at study entry. We compared the frequency of clinical manifestations and autoantibodies between aSLE and cSLE. For those with a significant difference, a multivariable logistic regression was performed, adjusting for ethnicity, SLE onset (cSLE vs aSLE), disease duration and centre. Disease activity and damage between aSLE and cSLE were compared after stratifying by disease duration. Results Of 552 aSLE subjects, 502 (90.9%) were female and 381 (69.0%) were Caucasian. Mean age at diagnosis was 37.0 ± 13.6 years and disease duration 10.9 ± 9.6 years. Of 276 cSLE subjects, 231 (83.7%) were female and 101 (36.6%) were Caucasian. Mean age at diagnosis was 12.7 ± 3.3 years and disease duration 5.6 ± 8.2 years. In multivariable regression analysis, aSLE was associated with decreased odds of having a neurologic disorder (odds ratio = 0.49) and increased odds of having aCL antibodies (odds ratio = 1.85). Disease activity and damage accrual scores were higher in aSLE than cSLE within the same disease duration strata, although the differences were not clinically significant. Ethnicity was not associated with any differences in clinical manifestations or autoantibody frequency between aSLE and cSLE. Conclusion Although a crude comparison of aSLE and cSLE yielded several differences in clinical symptoms and autoantibodies, this difference was not attributable to ethnic differences between aSLE and cSLE. [ABSTRACT FROM AUTHOR]

Objective: Currently there are 2 different classification criteria for systemic lupus erythematosus (SLE): American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC). The aim of this study was to compare the sensitivities of ACR and SLICC criteria in childhood-onset SLE (cSLE) using a large, multiethnic cohort.Methods: We conducted a retrospective study of 722 patients diagnosed with cSLE at The Hospital for Sick Children (SickKids). Prospectively collected data from SickKids' Lupus Database were reviewed/validated against medical records prior to ACR and SLICC scoring based on cumulative symptoms up to the last visit. Sensitivities were compared using McNemar's test. Descriptive statistics were used to identify SLE features unique to each set of criteria and autoantibodies not included in either.Results: ACR and SLICC sensitivities were as follows: 92.4% and 96.3% overall (p = 0.001); 82.5% and 91.3% (p = 0.01) in those scored ≤ 1 year from diagnosis; 92.7% and 97.9% (p = 0.02) in those scored 2-3 years from diagnosis. Forty-eight of 55 (87.3%) patients who did not meet ACR criteria met SLICC criteria through SLICC-specific criterion or renal biopsy. Twenty of 27 (74.1%) patients who did not meet SLICC criteria met ACR criteria as a result of photosensitivity (73.9%) and ACR lymphopenia criteria (26.1%). Six of 7 patients (85.7%) who were clinically diagnosed with cSLE but did not meet either SLICC or ACR criteria had anti-Ro antibodies.Conclusion: SLICC criteria were significantly more sensitive than ACR criteria in cSLE classification, especially early in the disease course. Because of the extreme rarity of primary Sjögren syndrome in children, one may consider adding anti-Ro antibodies to the classification criteria for cSLE because they are present in ∼40% of patents with cSLE. [ABSTRACT FROM AUTHOR]

Objective: End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long‐term kidney survival. This study was undertaken to identify short‐term end points that predict long‐term kidney outcomes for use in clinical trials. Methods: A database of 944 patients with LN was assembled from 3 clinical trials and 12 longitudinal cohorts. Variables from the first 12 months of treatment after diagnosis of active LN (prediction period) were assessed as potential predictors of long‐term outcomes in a 36‐month follow‐up period. The long‐term outcomes examined were new or progressive chronic kidney disease (CKD), severe kidney injury (SKI), and the need for permanent renal replacement therapy (RRT). To predict the risk for each outcome, hazard index tools (HITs) were derived using multivariable analysis with Cox proportional hazards regression. Results: Among 550 eligible subjects, 54 CKD, 55 SKI, and 22 RRT events occurred. Variables in the final CKD HIT were prediction‐period CKD status, 12‐month proteinuria, and 12‐month serum creatinine level. The SKI HIT variables included prediction‐period CKD status, International Society of Nephrology (ISN)/Renal Pathology Society (RPS) class, 12‐month proteinuria, 12‐month serum creatinine level, race, and an interaction between ISN/RPS class and 12‐month proteinuria. The RRT HIT included age at diagnosis, 12‐month proteinuria, and 12‐month serum creatinine level. Each HIT validated well internally (c‐indices 0.84–0.92) and in an independent LN cohort (c‐indices 0.89–0.92). Conclusion: HITs, derived from short‐term kidney responses to treatment, correlate with long‐term kidney outcomes, and now must be validated as surrogate end points for LN clinical trials. [ABSTRACT FROM AUTHOR]

Objective: No previous study has studied the longitudinal disease course of childhood-onset systemic lupus erythematosus (cSLE). Our objectives are to assess distinguishable differences in disease activity trajectories in cSLE patients, determine baseline factors predictive of disease trajectory membership, and assess if the different disease activity trajectories are associated with different damage trajectories.Methods: This is a retrospective, longitudinal inception cohort of cSLE patients. Patients were followed from diagnosis as children, until they were adults. SLE disease activity was modeled as a latent characteristic, jointly using the Systemic Lupus Erythematosus Disease Activity Index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors were tested for membership prediction of the latent classes of disease trajectories. Differences in damage trajectories by disease activity classes were tested using a mixed model.Results: A total of 473 patients (82% females), with median age at diagnosis of 14.1 years, were studied. We studied 11,992 visits (2,666 patient-years). We identified 5 classes of disease activity trajectories. Baseline major organ involvement, number of American College of Rheumatology criteria, and age at diagnosis predicted memberships into different classes. A higher proportion of Asians was in class 2 compared to class 5. Class 1 was associated with the most accrual of damage, while class 5 was associated with no significant damage accrual, even after 10 years.Conclusion: There are 5 distinct latent classes of disease trajectory in patients with cSLE. Membership within disease trajectories is predicted by baseline clinical and demographic factors. Membership in different disease activity trajectory classes is associated with different damage trajectories. [ABSTRACT FROM AUTHOR]

Objective: To determine the longitudinal damage trajectory of patients with juvenile-onset systemic lupus erythematosus (SLE), and to identify baseline and disease course predictors of damage trajectory.Methods: This is a retrospective inception cohort. Longitudinal pediatric-age data were obtained from a juvenile-onset SLE research database, while adult-age data were obtained from either a research database or patients' charts. Baseline factors were tested as predictors. Time-varying factors were lagged 6-24 months before a visit for testing their predictive effects. The longitudinal damage trajectory was modeled using a weighted generalized estimating equation.Results: This study cohort consisted of 473 subjects, with followup to 26 years. A total of 65% of patients were ages >18 years at last followup. Cataracts (14%), avascular necrosis (10%), and osteoporosis (5%) were the most common items of damage. Two patients had myocardial infarctions. Baseline features, self-reported ethnicity (Afro-Caribbean), earlier time periods of diagnosis, and the presence of a life-threatening major organ manifestation (lupus nephritis class III-V, cerebrovascular accidents, major organ vasculitis, pulmonary hemorrhage, or myocarditis), were associated with greater damage. Throughout the disease course, an acute confusional state, lupus headache, and fever predicted subsequent increases in the damage trajectory. A higher prednisone dose and exposure to cyclophosphamide also predicted subsequent increases in the damage trajectory. Antimalarial exposure was protective against an increase in damage trajectory.Conclusion: Patients with juvenile-onset SLE accrue damage steadily into adulthood. Baseline factors predict greater damage and/or influence the evolution of the damage trajectory. Additionally, SLE clinical features and therapies during the course of disease predict additional changes in the damage trajectory. [ABSTRACT FROM AUTHOR]

Objective. Recent studies have suggested that prenatal exposure to HCQ reduces the risk of cardiac neonatal lupus. The aim of this study is to assess if maternal intake of antimalarials (AMs) throughout pregnancy lowered the risk of cardiac and non-cardiac neonatal lupus. Methods. Consecutive children seen between 1 January 1984 to 1 October 2013 born to women with a CTD and positive anti-Ro and/or anti-La antibodies were eligible for this single-centre retrospective cohort study. A total of 315 individuals were screened and 268 participants were included. Exposure to AMs was defined as HCQ or chloroquine throughout pregnancy. Outcomes were cardiac and non-cardiac neonatal lupus. Frequentist and Bayesian analyses were performed. We hypothesized that prenatal AM exposure would decrease the risk of cardiac but not non-cardiac neonatal lupus. Results. A total of 268 pregnancies were included; 73 were exposed to AMs throughout pregnancy. Ninety-nine children developed neonatal lupus, 117 remained unaffected and 52 children did not develop cardiac neonatal lupus but could not be categorized as unaffected since their full non-cardiac neonatal lupus status was unknown. Logistic regression suggested a protective effect of AM on cardiac neonatal lupus, but results were not statistically significant [odds ratio (OR) 0.21; P = 0.07]. Bayesian analysis showed that the probability of obtaining a protective effect (OR<1.0) for cardiac neonatal lupus was significant (98.7%). The effect of AMs on non-cardiac neonatal lupus was not significant (OR 0.78; P = 0.21). Conclusion. In this large single-centre cohort study, exposure to AMs throughout pregnancy was asso- ciated with a decreased probability of developing cardiac but not non-cardiac neonatal lupus. [ABSTRACT FROM AUTHOR]

Most outcome studies of rheumatic diseases report outcomes ascertained on a single occasion. While single assessments are sufficient for terminal or irreversible outcomes, they may not be sufficiently informative if outcomes change or fluctuate over time. Consequently, longitudinal studies that measure non-terminal outcomes repeatedly afford a better understanding of disease evolution. Longitudinal studies require special analytic methods. Newer longitudinal analytic methods have evolved tremendously to deal with common challenges in longitudinal observational studies. In recent years, an increasing number of studies have used longitudinal design. This review aims to help readers understand and apply the findings from longitudinal studies. Using a cohort of children with juvenile dermatomyositis (JDM), we illustrate how to study evolution of disease activity in JDM using longitudinal methods. [ABSTRACT FROM AUTHOR]

Objective To determine whether longer disease duration negatively impacts carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and pulse wave velocity (PWV) in a cohort of patients with childhood-onset systemic lupus erythematosus (SLE), and to compare CIMT, FMD, and PWV in patients with childhood-onset SLE with those in healthy children and explore determinants of vascular test results in childhood-onset SLE. Methods Cross-sectional analysis was performed in a prospective longitudinal cohort of patients with childhood-onset SLE at the latest followup visit. Clinical and laboratory data were collected for patients with childhood-onset SLE. CIMT, FMD, and PWV were measured using standardized protocols in patients with childhood-onset SLE and healthy children. Correlations between disease duration and results of the 3 vascular tests were performed. Vascular data in patients with childhood-onset SLE were compared with those in healthy children. Multivariable linear regression was used to identify determinants of CIMT, FMD, and PWV in childhood-onset SLE. Results Patients with childhood-onset SLE (n = 149) and healthy controls (n = 178) were enrolled. The median age of the patients was 17.2 years (interquartile range [IQR] 15.7-17.9 years), and their median disease duration was 3.2 years (IQR 1.8-4.9 years). The median age of the healthy children was 14.7 years (IQR 13.1-15.9 years). Longer disease duration correlated with worse FMD (r = −0.2, P = 0.031) in patients with childhood-onset SLE. Patients with childhood-onset SLE had smaller (better) CIMT, higher (better) FMD, and similar PWV compared with healthy controls. Linear regression analysis explained <24% of the variation in vascular test results in patients with childhood-onset SLE, suggesting that other variables should be explored as important determinants of CIMT, FMD, and PWV. Conclusion In this cohort of 149 patients with childhood-onset SLE, patients did not have worse CIMT, FMD, or PWV than did healthy controls. Longer disease duration was associated with worse FMD, suggesting progressive endothelial dysfunction over time. [ABSTRACT FROM AUTHOR]

The article examines the ability of neutrophil gelatinase-associated lipocalin (NGAL) to predict worsening of renal disease activity in childhood-onset systemic lupus erythematosus (SLE). It highlights a longitudinal prospective study which was conducted to 111 patients with childhood-onset SLE. According to the article, serial measurement of urinary and plasma NGAL levels can be important in the prediction of global renal SLE disease activity.

Background/Purpose: Biologic therapies have revolutionized the management of rheumatic diseases of childhood. However, these medications are associated with adverse effects including the possible development of neoplasms. The aim of our study was to determine the rate as well as risk factors for the development of neoplasms in patients with JIA treated with biologics. Methods: We performed a retrospective review of the rheumatology biologic registry (RBR) at The Hospital for Sick Children (SickKids), Toronto, Canada, one of the largest quarternary pediatric referral centres in North America. Demographic and neoplastic data, clinical course and medication history were extracted from the RBR and clinical charts. Unless specified, data was expressed as median (IQR). The study was approved by the SickKids Ethics Review Board. Results: The cohort consisted of 357 patients with rheumatic diseases who were on one or more biologics between January 1997 and August 2013. Juvenile Idiopathic Arthritis (JIA) was the most common diagnosis [302/357 (84.5%)]. A total of 6/357 (1.68%) patients developed a neoplasm: 4 with JIA, 1 each with idiopathic uveitis and polyarteritis nodosa. (Refer to t87) [ABSTRACT FROM AUTHOR]

Background/Purpose: Macrophage activation syndrome (MAS), a life-threatening inflammatory emergency of children with rheumatic diseases, is increasingly recognized in pediatric systemic lupus erythematosus (pSLE). The challenge is to differentiate active pSLE from MAS in order to make correct treatment decisions. The purpose of this study is to generate a decision tree for the recognition of MAS in newly diagnosed pSLE and test the performance of these proposed criteria in an independent pSLE cohort. Methods: A retrospective cohort study of consecutive patients requiring admission to SickKids Hospital with newly diagnosed, active pSLE between January 2002 and July 2007 (training cohort) was performed. All patients met ≥4/11 ACR criteria. Data collection on: 1) Clinical features including fever, CNS dysfunction, splenomegaly, hepatomegaly and hemorrhage; 2) laboratory parameters; CBC, ESR, CRP, C3, C4, ferritin, AST, ALT, LDH, albumin, bilirubin, triglycerides, LDL, HDL, urea, creatinine, sodium, coagulation parameters including INR, PTT, fibrinogen and D-Dimer, and soluble IL-2 receptor (sIL-2R) and CD163. Patients were assigned to one of 2 cohorts exclusively (MAS/non-MAS). Putative predictor variables were compared between cohorts. A decision tree analysis for diagnosis of MAS in pSLE was constructed using recursive partitioning, and decision rules were subsequently applied to an independent cohort of newly diagnosed, active pSLE diagnosed and admitted to SickKids between July 2007 and July 2013 (testing cohort) to determine the sensitivity and specificity of the proposed criteria. Results: The training cohort consisted of 56 pSLE patients: 9 (16%) diagnosed with MAS and 47 non-MAS patients. Splenomegaly was more common in the non-MAS cohort, with no other differences in clinical characteristics between cohorts. Of all the available laboratory data, ALT ≥ 45 units/L, neutrophils < 1.65 × 103/mm3 and ferritin < 836 µg/L identified 56% of the patients with MAS (R2 = 0.75) with 100% specificity. The testing cohort consisted of 9 (20%) MAS and 37 non-MAS pSLE patients. The proposed thresholds for ALT, neutrophil count and ferritin demonstrated a sensitivity of 11% and specificity of 97%. Conclusion: MAS is a life threatening complication of pSLE. Early recognition is challenging yet critical for appropriate therapy. PSLE patient with and without MAS have many similar clinical and laboratory features. Using statistical modeling, the initial criteria developed maintained excellent specificity but poor sensitivity for distinguishing MAS from active SLE at diagnosis in the testing cohort. Hence, new validated models are required for the early recognition of MAS among pSLE patients. Future analyses are planned to address these issues. [ABSTRACT FROM AUTHOR]

Background/Purpose: 1) To determine the longitudinal disease activity trajectory of an inception cohort of Juvenile Dermatomyositis (JDM) patients, 2) To identify predictor(s) for longitudinal disease activity trajectory of JDM. Methods: A single-center, inception cohort of juvenile dermatomyositis (JDM) patients (age of diagnosis <18 years old), recruited within 1 year of their initial presentation was studied. The patients were accrued from January 1991 to December 2010, in a JDM subspecialty clinic. Patients were evaluated at every clinic visit for disease activity with the modified Disease Activity Score (mDAS). Baseline disease features-DASm, swallowing difficulty, skin ulcer, calcinosis, duration of symptoms before evaluation, age and gender-were evaluated as predictors of the longitudinal trajectory of JDM. Time-varying treatment effects were also tested. Longitudinal trajectory modeling was performed with mixed random effects modeling (random slopes). Results: Ninety-five JDM patients (33 males, 35%) were studied. The median age of onset was 7.8 (25th-75th percentile (P): 4.9-12.1) years. The median mDAS score at presentation was 7 (25th-75th P: 6-9), the median skin subscale score was 3 (25th-75th P: 2-4), the median musculoskeletal subscale was 4 (25th-75th P: 3-6). The median duration of follow-up was 4.6 (25th-75th P: 2.4-6.9) years. All patients in the cohort were treated with a standardized protocol comprising prednisone alone (before 2000) or methotrexate (MTX) and prednisone (after 2000). The disease trajectory of mDAS in this inception cohort followed a rapid reduction of activity within the first 2 years with a minor flare in disease activity beyond 2 years. Baseline nailfold abnormality predicted a slower improvement in mDAS trajectory. Higher baseline mDAS predicted faster improvement in mDAS trajectory. Treatment with MTX and prednisone predicted reductions in disease activity 3 and 6 months later respectively. Conclusion: Disease activity trajectory of JDM showed a general rapid reduction of mDAS followed by a small flare of disease activity beyond 2 years. Baseline nailfold abnormality and mDAS predicted future evolution of disease trajectory. The effects of treatment were observed only 3-6 months after. [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]

Objectives: The purpose of this study was to determine whether cardiac complications of neonatal lupus erythematosus (NLE) are related to maternal anti-Ro and anti-La autoantibody-levels. Background: Autoantibody-positive mothers are frequently referred for serial echocardiography because of the elevated fetal risk of developing immune-mediated heart block. Little is known why only some and not all offspring are affected. Methods: All cases referred since 2000 for serial fetal echocardiography or cardiac complications related to maternal antibodies were included. Patients without cardiac NLE (group 1) and with cardiac NLE (group 2) were compared. Antibody levels were measured by enzyme-linked immunosorbent assay with a cutoff value of 8 U/ml for a positive test result. Results: Group 1 included 146 serially screened fetuses with normal pregnancy outcomes. Group 2 consisted of 40 fetuses/neonates with a diagnosis of heart block or endocardial fibroelastosis or both, and included 4 fetuses diagnosed during serial screening. All cardiac complications were associated with moderate (≥50 U/ml; 15%) or high (≥100 U/ml; 85%) maternal anti-Ro levels, independently of anti-La antibody titres. The event rate of complete heart block was 5% for prospectively screened fetuses with Ro-values ≥50 U/ml (odds ratio: 7.8) and 0% for fetuses with lower titres (p < 0.0001). Infants with pre-natal exposure to high-titre anti-La levels ≥100 U/ml were the most likely to have noncardiac features of NLE (event rate: 57%; odds ratio: 4.7). Conclusions: Our findings support that the amount of maternal antibodies, rather than their presence, is associated with fetal tissue injury. As anti-Ro levels correlate with the risk of cardiac complications, serial echocardiography should be limited to women with high anti-Ro-titres. [Copyright &y& Elsevier]