Multisystem inflammatory syndrome in 1.2 million children: longitudinal cohort study of risk factors.

BACKGROUND: We identified patient characteristics associated with an increased risk of developing MIS-C. METHODS: We conducted a longitudinal cohort study of 1,195,327 patients aged 0-19 years between 2006 and 2021, including the first two waves of the pandemic (February 25-August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders. RESULTS: Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61-22.6), atopic conditions (RR 3.34, 95% CI 1.60-6.97), and cancer (RR 8.11, 95% CI 1.13-58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development. CONCLUSIONS: Children with pre-existing morbidity have a considerably elevated risk of MIS-C. IMPACT: Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear. In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C. Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C. Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication.

Maternal autoimmune disease and risk of hospitalization for autoimmune disease, allergy, and cancer in offspring.

BACKGROUND: Children whose mothers have autoimmune disease may be at risk of developing immune-mediated disorders. We assessed the association between maternal autoimmune disease and risk of autoimmune disease, allergy, and cancer in offspring. METHODS: We analyzed a cohort of 1,011,623 children born in Canada between 2006 and 2019. We identified mothers who had autoimmune diseases and assessed hospitalizations for autoimmune disease, allergy, and cancer in offspring between birth and 14 years of age. We estimated hazard ratios (HR) for the association of maternal autoimmune disease with child hospitalization in adjusted Cox regression models. We used within-sibling analysis to control for genetic and environmental confounders. RESULTS: A total of 20,354 children (2.0%) had mothers with an autoimmune disease. Compared with no autoimmune disease, maternal autoimmune disease was associated with the risk of childhood hospitalization for autoimmune disease (HR 1.96, 95% CI 1.66-2.31) and allergy (HR 1.30, 95% CI 1.21-1.40), but was not significantly associated with cancer (HR 1.31, 95% CI 0.96-1.80). Type 1 diabetes, celiac disease, inflammatory arthritis, and systemic lupus erythematosus were among specific maternal autoimmune diseases most strongly associated with childhood hospitalization for autoimmune disease and allergy. The associations disappeared after controlling for genetic and environmental confounders in the within-sibling analysis. CONCLUSIONS: Maternal autoimmune disease is associated with an increased risk of autoimmune disease and allergy hospitalization in offspring, but the relationship appears to be confounded by genetic and environmental factors. Prenatal exposure to immunologic or pharmacologic products is not likely a direct cause of immune-mediated disease in children.

Cesarean delivery and risk of hospitalization for autoimmune disorders before 14 years of age.

It is supposed that cesarean birth is implicated in the development of autoimmunity. We evaluated the association between cesarean delivery and the risk of hospitalization for autoimmune disease in children up to 14 years of age. We performed a longitudinal cohort study of 934,873 children born between 2006 and 2019 in Quebec, Canada. The main exposure measure was cesarean delivery versus vaginal delivery (spontaneous or induced). Outcomes included hospitalization for type 1 diabetes, celiac disease, or other autoimmune disorders before 14 years of age. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between cesarean delivery and hospitalization for autoimmune disorders, adjusted for patient characteristics. A total of 248,963 children (27%) were delivered by cesarean. Median length of follow-up was 7.4 years. The hospitalization rate for autoimmune disorders was 69.1 per 100,000 person-years for cesarean and 65.9 per 100,000 person-years for vaginal delivery. Cesarean delivery was not associated with autoimmune disorders overall (HR 1.02, 95% CI 0.96-1.10). There was no association with type 1 diabetes (HR 1.00, 95% CI 0.85-1.17), celiac disease (HR 0.86, 95% CI 0.71-1.04), inflammatory bowel disease (HR 1.15, 95% CI 0.88-1.49), or idiopathic thrombocytopenic purpura (HR 1.01, 95% CI 0.82-1.25). Cesarean delivery was not associated with autoimmune disorders at different ages.Conclusion: This study suggests that cesarean delivery is not associated with the risk of hospitalization for autoimmune disorders before 14 years of age. Delivery mode does not seem to mediate the risk of autoimmunity in childhood. What is Known: • Children born by cesarean may be at risk of abnormal immune development. • The association between cesarean delivery and risk of pediatric autoimmune disorders is unclear. What is New: • In this cohort study of over 900,000 children, cesarean delivery was not associated with the risk of hospitalization for a range of autoimmune disorders before 14 years of age. • Cesarean delivery may not be related to the development of autoimmunity.

Maternal Autoimmune Disorders and Risk of Kawasaki Disease in Offspring.

We assessed the association between maternal autoimmune disorders and offspring risk of Kawasaki disease in a longitudinal cohort of 792 108 newborns. We found that maternal autoimmune disorders, especially autoimmune thyroiditis, may be risk factors for Kawasaki disease in children, particularly young children.

Multisystem inflammatory syndrome in adults: Comparison with other inflammatory conditions during the Covid-19 pandemic.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is an increasingly recognized complication of Covid-19. We assessed risk factors, clinical characteristics, and outcomes of patients with MIS-A compared with other inflammatory conditions. METHODS: We analyzed a cohort of patients ≥21 years hospitalized with MIS-A in Quebec, Canada between February 2020 and March 2021. We included comparison groups that share symptomatology or pathophysiology with MIS-A, including Kawasaki disease, toxic shock syndrome, and other Covid-19 complications. We examined characteristics of men and women at admission, and identified preexisting factors associated with MIS-A through odds ratios (OR) and 95% confidence intervals (CI) from adjusted logistic regression models. RESULTS: Among 22,251 patients in this study, 52 had MIS-A, 90 Kawasaki disease, 500 toxic shock syndrome, and 21,609 other Covid-19 complications. MIS-A was associated with an elevated risk of respiratory failure compared with Kawasaki disease (OR 7.22, 95% CI 1.26-41.24), toxic shock syndrome (OR 4.41, 95% CI 1.73-11.23), and other Covid-19 complications (OR 3.03, 95% CI 1.67-5.50). Patients with MIS-A had a greater risk of cardiac involvement, renal failure, and mortality. The data pointed towards sex-specific differences in presentation, with more respiratory involvement in women and cardiac involvement in men compared with patients that had other Covid-19 complications. Except for allergic disorders and cancer, prior medical risk factors were not associated with a greater likelihood of MIS-A. CONCLUSIONS: Patients with MIS-A have an elevated risk of mortality compared with other inflammatory conditions, with women having a predominance of respiratory complications and men cardiovascular complications.

Evaluation of the clinimetric properties of the Early Inflammatory Arthritis--self-administered comorbidity questionnaire.

OBJECTIVES: To adapt the self-administered comorbidity questionnaire (SCQ) into the Early Inflammatory Arthritis-SCQ (EIA-SCQ) and assess its clinimetric properties in EIA. METHODS: The EIA-SCQ and indices of disease activity, function, pain, health-related quality of life (HRQoL) and health resource utilization were administered to 320 patients with EIA. Twenty patients completed the EIA-SCQ a second time 1 week later. Construct validity was evaluated by testing the hypotheses that a valid comorbidity index would correlate well with age, weakly with HRQoL and recent resource utilization and poorly with indices of disease activity, function and pain. RESULTS: The intra-class correlation coefficient between repeat scores was 0.93 (95% CI 0.83-0.97). Kappa values for individual items ranged from 0.64 to 1.0. EIA-SCQ scores correlated moderately with age (Tau B = 0.29, P < 0.001) and weakly with function (HAQ-DI Tau B = 0.09, P = 0.03), pain (McGill Pain Questionnaire Tau B = 0.09, P = 0.05), some measures of HRQoL [the SF-36 mental component score (MCS) Tau B = - 0.08, P < 0.05; World Health Organization Disease Assessment Schedule II score Tau B = 0.09, P = 0.03] and a measure of resource utilization (number of tests in the last 4 months Tau B = 0.10, P = 0.04). The EIA-SCQ did not correlate with other measures of disease activity, another HRQoL measure [SF-36 physical component score (PCS)] or other measures of resource utilization. CONCLUSIONS: The EIA-SCQ is reliable and valid for use in EIA. It has the potential to become a useful measure of comorbidity in outcome studies of EIA when the resources for a full medical chart review are unavailable.

Symptoms of depression predict the trajectory of pain among patients with early inflammatory arthritis: a path analysis approach to assessing change.

OBJECTIVE: To assess the longitudinal relationships, including directionality, among chronic pain, symptoms of depression, and disease activity in patients with early inflammatory arthritis (EIA). METHODS: One hundred eighty patients with EIA completed an examination, including swollen joint count, and were administered the Center for Epidemiological Studies Depression Scale (CES-D) and the McGill Pain Questionnaire (MPQ) at 2 timepoints 6 months apart. Cross-lagged panel path analysis was used to simultaneously assess concurrent and longitudinal relationships among pain, symptoms of depression, and number of swollen joints. RESULTS: Pain, symptoms of depression, and number of swollen joints decreased over time (p < 0.001) and were prospectively linked to pain, symptoms of depression, and number of swollen joints, respectively, at 6 months. Symptoms of depression and pain were correlated with each other at baseline (0.47) and at 6-month followup assessments (0.28). Baseline symptoms of depression significantly predicted pain symptoms at 6 months (standardized regression coefficient = 0.28, p = 0.001), whereas pain and disease activity did not predict the course of any other variable after controlling for baseline values. CONCLUSION: Symptoms of depression predicted the trajectory of pain from baseline to 6 months. In addition, there were reciprocal/bidirectional associations between pain and symptoms of depression over time. More research is needed to better understand the relationship between pain and depressive symptoms and how to best manage patients with EIA who have high levels of both.

The clinimetric properties of the World Health Organization Disability Assessment Schedule II in early inflammatory arthritis.

OBJECTIVE: To assess the clinimetric properties of a new health-related quality of life (HRQOL) instrument, the World Health Organization Disability Assessment Schedule II (WHODAS II), in patients with early inflammatory arthritis. METHODS: Internal consistency as well as criterion, construct, and discriminative validity of the WHODAS II were assessed in 172 patients with early inflammatory arthritis who completed the WHODAS II, the Medical Outcomes Study Short Form 36 (SF-36), and other measures of disease severity, functioning, pain, depression, and resource use. Test-retest reliability of the WHODAS II was assessed by having a subset of 20 patients complete the WHODAS II a second time, 1 week after the first assessment. RESULTS: The WHODAS II had high internal consistency (Cronbach's alpha = 0.96 for patients working or in school and 0.93 for patients not working or in school). Test-retest intraclass correlation coefficients of the WHODAS II total score and subscales ranged from 0.82-0.96. The WHODAS II total score was strongly correlated with the SF-36 physical component score (Kendall's tau-b 0.51, P < 0.001) and moderately correlated with the SF-36 mental component score (tau-b 0.43, P < 0.001). WHODAS II correlations with disease outcomes ranged from Kendall's tau-b 0.15-0.55. The WHODAS II significantly differentiated between every aspect of disease severity assessed with the exception of measures of health resource use. CONCLUSION: The WHODAS II is a valid and reliable measure of HRQOL in cross-sectional studies of patients with early inflammatory arthritis. Research is still required to investigate potential item redundancy and determine its usefulness in longitudinal studies.