Pre-pregnancy maternal cardiovascular diseases and risk of offspring’s neurodevelopmental disorders: a population-based cohort study.

Objective Maternal exposure to cardiovascular disease (CVD) is associated with adverse maternal and neonatal health outcomes. However, its association with offspring’s long-term neurodevelopmental disorders (NDDs) is not yet known. We aimed to investigate the association between maternal pre-existing CVDs and children’s NDDs. Approach This nationwide cohort study included 2.7 million live singleton births recorded in the Swedish Medical Birth Register between 1990 and 2019. Information on maternal pre-pregnancy CVDs was extracted from the National Patient Register, including diagnosis of cerebrovascular disease, heart failure, arrhythmia, valvular and congenital heart diseases. Registered diagnoses of offspring NDDs included Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and intellectual disability. Cox proportional hazards models were fitted to estimate Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) for the associations. All estimates were adjusted for offspring’s age at diagnosis, sex, calendar period, and maternal characteristics including age at birth, parity, education, country of birth, cohabitation status, smoking, psychiatric illness, pre-gestational diabetes, and hypertension. Results The overall prevalence of maternal CVDs was 0.8% between 1990 and 2019. A total of 141 651 individuals (5.2%) received a diagnosis of ADHD, 64 691 (2.4%) of ASD, and 22 913 (0.9%) received a diagnosis of intellectual disability. The adjusted analyses showed that offspring of mothers with CVD had 16% higher rate of ADHD (HR 1.16; 95% CI: 1.09-1.24) and 12% higher rate of ASD (HR 1.12; 95% CI: 1.02-1.23), compared with offspring of mothers without CVD. Specifically, maternal heart failure was associated with 1.93-fold increased HR of ASD (95% CI: 1.21-3.08), maternal arrhythmia with 14% increased rate of ADHD (95% CI: 1.04-1.24), and maternal cerebrovascular disease was associated with 30% elevated rate of ASD (95% CI: 1.07-1.59) and 17% elevated rate of ADHD (95% CI: 1.02-1.36). No association was found between maternal CVDs and intellectual disability. Conclusion Maternal CVD before pregnancy may be a risk factor for offspring’s ADHD and ASD, with varied risks by CVD subtypes. The mechanisms behind the associations warrant further investigations

Risk Factors Associated with the Onset of Relapsing-Remitting and Primary Progressive Multiple Sclerosis: A Systematic Review

Multiple sclerosis (MS) is a chronic central nervous system disease with a highly heterogeneous course. The aetiology of MS is not well understood but is likely a combination of both genetic and environmental factors. Approximately 85% of patients present with relapsing-remitting MS (RRMS), while 10–15% present with primary progressive MS (PPMS). PPMS is associated with an older onset age, a different sex ratio, and a considerably more rapid disease progression relative to RRMS. We systematically reviewed the literature to identify modifiable risk factors that may be associated with these different clinical courses. We performed a search of six databases and integrated twenty observational studies into a descriptive review. Exposure to Epstein-Barr virus (EBV) appeared to increase the risk of RRMS, but its association with PPMS was less clear. Other infections, such as human herpesvirus-6 and chlamydia pneumoniae, were not consistently associated with a specific disease course nor was cigarette smoking. Despite the vast literature examining risk factors for the development of MS, relatively few studies reported findings by disease course. This review exposes a gap in our understanding of the risk factors associated with the onset of PPMS, our current knowledge being predominated by relapsing-onset MS

Cholesterol and markers of cholesterol turnover in multiple sclerosis: Relationship with disease outcomes

Multiple sclerosis (MS) is a chronic central nervous system disease that is associated with progressive loss of myelin and subsequent axonal degeneration. Cholesterol is an essential component of mammalian cellular and myelin membranes. In this systematic review, we examined the relationship between levels of cholesterol and markers of cholesterol turnover in circulation and/or cerebrospinal fluid (CSF) and disease outcomes in adults with clinically isolated syndrome (CIS) or confirmed MS. Studies suggest that elevated levels of circulating low density lipoprotein cholesterol (LDL), total cholesterol, and particularly, apolipoprotein B and oxidized LDL are associated with adverse clinical and MRI outcomes in MS. These relationships were observed as early as CIS. The studies also suggest that oxysterols, cholesterol precursors, and apolipoprotein E may be markers of specific disease processes in MS, but more research is required to elucidate these processes and relationships. Taken together, the data indicate that cholesterol and markers of cholesterol turnover have potential to be used clinically as biomarkers of disease activity and may even be implicated in the pathogenesis of MS

A population-based study comparing multiple sclerosis clinic users and non-users in British Columbia, Canada

ABSTRACT Objectives Much clinical knowledge about multiple sclerosis (MS) has been gained from patients who attend MS specialty clinics. However, there is limited information about whether these patients are representative of the wider MS population. The objective of this study was to compare incident MS cases who were MS clinic users to non-users of the specialty MS clinics in British Columbia, Canada. Approach This was a retrospective record linkage cohort study using prospectively collected data from the BCMS database and province-wide health administrative databases. Incident MS cases were identified in the general population using a validated algorithm of hospital and physician diagnostic codes. Results There were 2,841 incident MS cases between 1996 and 2004 including 1,648 (58%) that had registered at an MS clinic (‘clinic cases’) and 1,193 (42%) that had not (‘non-clinic cases’). Sex and socioeconomic status distributions were similar; however, non-clinic cases were older, accessed health services more frequently, and had a higher burden of comorbidity than clinic cases. Only 1% of the non-clinic cases had filled a prescription for an MS-specific disease-modifying therapy, compared to 51% of the clinic cases. Conclusion Our findings have several important implications: even within a publicly funded healthcare system, a high proportion of individuals with MS may not access a specialty MS clinic; the needs of MS patients managed in the community may differ from those referred to an MS clinic; findings from studies involving clinic-based MS cohorts may not always be generalizable to the wider MS population; and access to population-based health administrative data offers the opportunity to gain a broader understanding of MS

Validating the diagnosis of multiple sclerosis using Swedish administrative data in Värmland County

Objectives: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. Identifying MS at the population level is important for disease surveillance and allocation of resources. The Swedish National Patient Registry (NPR) has been used to study the epidemiology of MS, but the accuracy of this resource is not known. We aimed to validate a definition of MS using the Swedish NPR in Varmland County using a longitudinal cohort design. Materials and Methods: Data were extracted from the NPR, the Total Population Register, the Swedish MS Register, and medical records for the years 2001-2013. Fifteen algorithms of hospitalizations and clinic visits for MS were developed and compared with findings in medical records, which acted as the "gold standard" definition. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were estimated. Results: Of 805 eligible persons identified in the NPR, 763 had MS (94.8%) according to medical records. Of these, 544 (71.3%) were also registered in the SMSreg. The case definition that had a well-balanced sensitivity and specificity required three or more clinic or hospital visits for MS (sensitivity of 85.3% (95% CI: 82.6-87.8) and specificity of 81.0% (95%CI: 65.9-91.4). Conclusions: Multiple case definitions with high sensitivity and moderate specificity were found, suggesting that the NPR can be used to accurately identify persons with MS

Adverse health behaviours are associated with depression and anxiety in multiple sclerosis: A prospective multisite study

Rx & D Health Research FoundationDon Paty Career Development Award from the MS Society of Canadapostdoctoral fellowship from the Multiple Sclerosis Society of CanadaAlistair M. Fraser Master Studentship from the Multiple Sclerosis Society of CanadaBackground: Depression and anxiety are common among people with multiple sclerosis (MS), as are adverse health behaviours, but the associations between these factors are unclear. Objective: To evaluate the associations between cigarette smoking, alcohol use, and depression and anxiety in MS in a cross-Canada prospective study. Methods: From July 2010 to March 2011 we recruited consecutive MS patients from four MS clinics. At three visits over two years, clinical and demographic information was collected, and participants completed questionnaires regarding health behaviours and mental health. Results: Of 949 participants, 75.2% were women, with a mean age of 48.6 years; most had a relapsing-remitting course (72.4%). Alcohol dependence was associated with increased odds of anxiety (OR: 1.84; 95% CI: 1.32-2.58) and depression (OR: 1.53; 95% CI: 1.05-2.23) adjusting for age, sex, Expanded Disability Status Scale (EDSS), and smoking status. Smoking was associated with increased odds of anxiety (OR: 1.29; 95% CI: 1.02-1.63) and depression (OR: 1.37; 95% CI: 1.04-1.78) adjusting for age, sex, EDSS, and alcohol dependence. Alcohol dependence was associated with an increased incidence of depression but not anxiety. Depression was associated with an increased incidence of alcohol dependence. Conclusion: Alcohol dependence and smoking were associated with anxiety and depression. Awareness of the effects of adverse health behaviours on mental health in MS might help target counselling and support for those 'at risk'.Canadian Institutes of Health Researc