Omega-3 Index, fish consumption, use of fish oil supplements and first clinical diagnosis of central nervous system demyelination

Higher intakes of omega-3 polyunsaturated fatty acids (n3PUFAs) have been associated with lower MS risk. We aimed to test associations between the Omega-3 Index, blood levels of n3PUFAs, fish oil supplement use, and fish consumption with a first clinical diagnosis of CNS demyelination (FCD). Cases (n = 250) had a higher Omega-3 Index compared with a matched group of controls (n = 471) (average treatment effect (ATE)=0.31, p = 0.047, based on augmented inverse probability weighting). A higher percentage of cases than controls used fish oil supplements (cases=17% vs. controls=10%). We found that Omega-3 Index increased as time between FCD and study interview increased (e.g., at or below median (112 days), based on ATE, mean=5.30, 95% CI 5.08, 5.53; above median, mean=5.90, 95% CI 5.51, 6.30). Fish oil supplement use increased in a similar manner (at or below median (112 days), based on ATE, proportion=0.12, 95% CI 0.06, 0.18; above the median, proportion=0.21, 95% CI 0.14, 0.28). Our results suggest a behaviour change post FCD with increased use of fish oil supplements

Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein–Barr virus

OnlinePublBackground and purpose: Epstein–Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. Methods: In the Ausimmune case–control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZVDNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein–Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates. Results: In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08–4.46, p= 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS riskrelated human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 106 copies/mL). Conclusions: HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/ management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.Robyn M. Lucas, Meav-Lang J. Lay, James Grant, Nicolas Cherbuin, Cheryl S. Toi, Keith Dear, Bruce V. Taylor, Dominic E. Dwyer, Ausimmune Investigator Group, Anne-Louise Ponsonb

A pro-inflammatory diet in people with multiple sclerosis is associated with an increased rate of relapse and increased FLAIR lesion volume on MRI in early multiple sclerosis: A prospective cohort study

First published online May 6, 2023Background: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS. Objective: We examined whether Dietary Inflammatory Index (DII®)) scores are associated with measures of MS progression and inflammatory activity. Methods: A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n=223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DIITM) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures; fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume. Results: A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio=2.24, 95% confidence interval (CI)= −1.16, 4.33, p=0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (β=0.38, 95% CI=0.04, 0.72, p=0.03). Conclusion: There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.Alice M Saul, Bruce V Taylor, Leigh Blizzard, Steve Simpson-Yap, Wendy H Oddy, Nittin Shivappa, James R Hébert, Lucinda J Black, Anne-Louise Ponsonby, Simon A Broadley, Jeanette Lechner-Scott and Ingrid van der Mei, Ausimmune, AusLong Investigators Grou

Harmonizing analytical chemistry and clinical epidemiology for human biomonitoring studies. A case-study of plastic product chemicals in urine

There is an interdisciplinary interface between analytical chemistry and epidemiology studies with respect to the design, execution, and analysis of environmental epidemiology cohorts and studies. Extracting meaningful results linking chemical exposure to human health outcomes begins at study design and spans the entire workflow. Here we discuss analytical experimental design from an exposure science perspective, and propose a reporting checklist for the design of human biomonitoring studies. We explain key analytical chemistry concepts of blanks and limits of reporting and present a case series of plastic product chemical exposure in prenatal urine specimens from the Barwon Infant Study

Swaddling and the Risk of Sudden Infant Death Syndrome: A Meta-analysis

CONTEXT: Swaddling is a traditional practice of wrapping infants to promote calming and sleep. Although the benefits and risks of swaddling in general have been studied, the practice in relation to sudden infant death syndrome remains unclear. OBJECTIVE: The goal of this study was to conduct an individual-level meta-analysis of sudden infant death syndrome risk for infants swaddled for sleep. DATA SOURCES: Additional data on sleeping position and age were provided by authors of included studies. STUDY SELECTION: Observational studies that measured swaddling for the last or reference sleep were included. DATA EXTRACTION: Of 283 articles screened, 4 studies met the inclusion criteria. RESULTS: There was significant heterogeneity among studies (I(2) = 65.5%; P = .03), and a random effects model was therefore used for analysis. The overall age-adjusted pooled odds ratio (OR) for swaddling in all 4 studies was 1.58 (95% confidence interval [CI], 0.97-2.58). Removing the most recent study conducted in the United Kingdom reduced the heterogeneity (I(2) = 28.2%; P = .25) and provided a pooled OR (using a fixed effects model) of 1.38 (95% CI, 1.05-1.80). Swaddling risk varied according to position placed for sleep; the risk was highest for prone sleeping (OR, 12.99 [95% CI, 4.14-40.77]), followed by side sleeping (OR, 3.16 [95% CI, 2.08-4.81]) and supine sleeping (OR, 1.93 [95% CI, 1.27-2.93]). Limited evidence suggested swaddling risk increased with infant age and was associated with a twofold risk for infants aged >6 months. LIMITATIONS: Heterogeneity among the few studies available, imprecise definitions of swaddling, and difficulties controlling for further known risks make interpretation difficult. CONCLUSIONS: Current advice to avoid front or side positions for sleep especially applies to infants who are swaddled. Consideration should be given to an age after which swaddling should be discouraged

Higher levels of reported sun exposure, and not vitamin D status, are associated with less depressive symptoms and fatigue in multiple sclerosis

ObjectiveInsufficient sun exposure and vitamin D deficiency have both been associated with increased risk of multiple sclerosis (MS). Depressi on, anxiety, fatigue and cognitive impairment are prevalent and disabling symptoms in MS. Our objective was to examine the associations between personal sun exposure and serum 25-hydroxyvitamin D (25(OH)D), and depression, anxiety, fatigue and cognition. MethodsA total of 198 participants with multiple sclerosis were followed prospectively for an average of 2.3years. Assessments of serum 25(OH)D, sun exposure, depression, anxiety and fatigue were carried out biannually; cognition was assessed annually. ResultsPersonal reported sun exposure was inversely associated with depression scores ( -0.26 (95%CI -0.40, -0.12);P0.001) and fatigue scores ( -0.65 (95%CI -1.23, -0.07); P=0.028). Only high levels of 25(OH)D (>80nm) were inversely associated depression scores ( -0.64 (95%CI -1.15, -0.13); P=0.015), but this was not significant after adjustment for reported sun exposure. No associations were seen between reported sun exposure or serum 25(OH)D levels and anxiety or cognition scores. ConclusionWe found that higher levels reported sun exposure, rather than 25(OH)D levels, were associated with less depressive symptoms and levels of fatigue. The role of UV or light therapy will need to be evaluated in randomized controlled trials to confirm an effect on these symptoms in MS

Sun exposure and vitamin D are independent risk factors for CNS demyelination

Objectives: To examine whether past and recent sun exposure and vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] levels) are associated with risk of first demyelinating events (FDEs) and to evaluate the contribution of these factors to the latitudinal gradient in FDE incidence in Australia. Methods: This was a multicenter incident case-control study. Cases (n = 216) were aged 18-59 years with a FDE and resident within one of 4 Australian centers (from latitudes 27°S to 43°S), from November 1, 2003, to December 31, 2006. Controls (n = 395) were matched to cases on age, sex, and study region, without CNS demyelination. Exposures measured included self-reported sun exposure by life stage, objective measures of skin phenotype and actinic damage, and vitamin D status. Results: Higher levels of past, recent, and accumulated leisure-time sun exposure were each associated with reduced risk of FDE, e.g., accumulated leisure-time sun exposure (age 6 years to current), adjusted odds ratio (AOR) = 0.70 (95% confidence interval [CI] 0.53-0.94) for each ultraviolet (UV) dose increment of 1,000 kJ/m (range 508-6,397 kJ/m). Higher actinic skin damage (AOR = 0.39 [95% CI 0.17-0.92], highest grade vs the lowest) and higher serum vitamin D status (AOR = 0.93 [95% CI 0.86-1.00] per 10 nmol/L increase in 25(OH)D) were independently associated with decreased FDE risk. Differences in leisure-time sun exposure, serum 25(OH)D level, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions. Conclusions: Sun exposure and vitamin D status may have independent roles in the risk of CNS demyelination. Both will need to be evaluated in clinical trials for multiple sclerosis prevention. Copyrigh

Anxiety, depression and fatigue at 5-year review following CNS demyelination

BACKGROUND: Anxiety and depression are common in multiple sclerosis (MS). We evaluated the prevalence and factors associated with anxiety, depression and fatigue at the 5-year review of a longitudinal cohort study following a first clinical diagnosis of CNS demyelination (FCD). METHODS: Cases with a FCD were recruited soon after diagnosis and followed annually thereafter. A variety of environmental, behavioural and clinical covariates were measured at five-year review. Anxiety and depression were measured using the Hospital Anxiety & Depression Scale (HADS), and fatigue by the Fatigue Severity Scale (FSS). RESULTS: Of the 236 cases, 40.2% had clinical anxiety (median HADS-A: 6.0), 16.0% had clinical depression (median HADS-D: 3.0), and 41.3% had clinical fatigue (median FSS: 4.56). The co-occurrence of all three symptoms was 3.76 times greater than expectation. Younger age, higher disability, concussion or other disease diagnosis were independently associated with a higher anxiety score; male sex, higher disability, being unemployed, less physical activity, and antidepressant and/or anxiolytic-sedative medication use were independently associated with a higher depression score. Higher disability, immunomodulatory medication use, other disease diagnosis and anxiolytic-sedative medication use were independently associated with having fatigue, while female sex, higher BMI, having had a concussion, being unemployed and higher disability were associated with a higher fatigue score. CONCLUSION: These results support previous findings of the commonality of anxiety, depression and fatigue in established MS and extend this to post-FCD and early MS cases. The clustering of the three symptoms indicates that they may share common antecedents

Early life infection and proinflammatory, atherogenic metabolomic and lipidomic profiles in infancy: a population-based cohort study

BACKGROUND: The risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous in infancy and induces inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood remains unexplored. We investigated relationships between infection and plasma metabolomic and lipidomic profiles at age 6 and 12 months, and mediation of these associations by inflammation. METHODS: Matched infection, metabolomics, and lipidomics data were generated from 555 infants in a pre-birth longitudinal cohort. Infection data from birth to 12 months were parent-reported (total infections at age 1, 3, 6, 9, and 12 months), inflammation markers (high-sensitivity C-reactive protein [hsCRP]; glycoprotein acetyls [GlycA]) were quantified at 12 months. Metabolic profiles were 12-month plasma nuclear magnetic resonance metabolomics (228 metabolites) and liquid chromatography/mass spectrometry lipidomics (776 lipids). Associations were evaluated with multivariable linear regression models. In secondary analyses, corresponding inflammation and metabolic data from birth (serum) and 6-month (plasma) time points were used. RESULTS: At 12 months, more frequent infant infections were associated with adverse metabolomic (elevated inflammation markers, triglycerides and phenylalanine, and lower high-density lipoprotein [HDL] cholesterol and apolipoprotein A1) and lipidomic profiles (elevated phosphatidylethanolamines and lower trihexosylceramides, dehydrocholesteryl esters, and plasmalogens). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA mediated a substantial proportion of the relationship between infection and metabolome/lipidome, with hsCRP generally mediating a lower proportion. Analogous relationships were observed between infection and 6-month inflammation, HDL cholesterol, and apolipoprotein A1. CONCLUSIONS: Infants with a greater infection burden in the first year of life had proinflammatory and proatherogenic plasma metabolomic/lipidomic profiles at 12 months of age that in adults are indicative of heightened risk of cardiovascular disease, obesity, and type 2 diabetes. These findings suggest potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk. FUNDING: The establishment work and infrastructure for the BIS was provided by the Murdoch Children's Research Institute (MCRI), Deakin University, and Barwon Health. Subsequent funding was secured from National Health and Medical Research Council of Australia (NHMRC), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O'Brien Memorial Asthma Foundation, the Our Women's Our Children's Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Minderoo Foundation, the Ilhan Food Allergy Foundation, GMHBA, Vanguard Investments Australia Ltd, and the Percy Baxter Charitable Trust, Perpetual Trustees. In-kind support was provided by the Cotton On Foundation and CreativeForce. The study sponsors were not involved in the collection, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication. Research at MCRI is supported by the Victorian Government's Operational Infrastructure Support Program. This work was also supported by NHMRC Senior Research Fellowships to ALP (1008396); DB (1064629); and RS (1045161) , NHMRC Investigator Grants to ALP (1110200) and DB (1175744), NHMRC-A*STAR project grant (1149047). TM is supported by an MCRI ECR Fellowship. SB is supported by the Dutch Research Council (452173113)