Vitamin D Status During Pregnancy and Risk of Multiple Sclerosis in Offspring of Women in the Finnish Maternity Cohort

IMPORTANCE Vitamin D has been associated with a decreased risk of multiple sclerosis (MS) in adulthood; however, some, but not all, previous studies have suggested that in utero vitamin D exposure may be a risk factor forMS later in life. OBJECTIVE To examine whether serum 25-hydroxyvitamin D (25[OH]D) levels in early pregnancy are associated with risk of MS in offspring. DESIGN, SETTING, AND PARTICIPANTS Prospective, nested case-control study in the Finnish Maternity Cohort conducted in May 2011.We identified 193 individuals with a diagnosis of MS before December 31, 2009, whose mothers are in the Finnish Maternity Cohort and had an available serum sample from the pregnancy with the affected child.We matched 176 cases with 326 controls on region of birth in Finland, date of maternal serum sample collection, date of mother’s birth, and date of child’s birth. MAIN OUTCOMES AND MEASURES Maternal serum 25(OH)D levelswere measured using a chemiluminescence assay. The risk of MS among offspring and association with maternal 25(OH)D levels were the main outcomes. Conditional logistic regression was used and further adjusted for sex of the child, gestational age at the time of sample collection, and season of sample collection to estimate the relative risks and 95%CIs. RESULTS Of the 193 cases in the study, 163 were female. Of the 331 controls in the study, 218 were female. Seventy percent of serum samples were collected during the first trimester of pregnancy. The mean (SD) maternal vitamin D levels were in the insufficient vitamin D range, but higher in maternal control than case samples (15.02 [6.41] ng/mL vs 13.86 [5.49] ng/mL [to convert to nanomoles per liter, multiply by 2.496]). Maternal vitamin D deficiency (25[OH]D levels increased risk of MS in the offspring (relative risk, 1.90; 95%CI, 1.20-3.01; P = .006) compared with women who did not have deficient 25(OH)D levels. There was no statistically significant association between the risk of MS and increasing serum 25(OH)D levels (P = .12). CONCLUSIONS AND RELEVANCE Insufficient maternal 25(OH)D during pregnancymay increase the risk of MS in offspring</p

Molecular mechanism underlying the impact of vitamin D on disease activity of MS

Objective: Some previous studies suggest modest to strong effects of 25-hydroxyvitamin D (25(OH)D) on multiple sclerosis (MS) activity. The objective of this study was to explore the mechanistic rationale that may explain potential clinical effects of 25(OH)D. Methods: This study measured serum 25(OH)D levels and global gene expression profiles over a course of up to 2 years in patients starting treatment with interferon beta-1b (IFNB-1b) after a clinically isolated syndrome. MS disease activity was assessed by the number of gadolinium-enhancing lesions present on repeated magnetic resonance imaging (MRIs). Results: The number of gadolinium-enhancing lesions was highly significantly associated with 25(OH)D levels. Conducting various systems-level analyses on the molecular level, multiple lines of evidence indicated that 25(OH)D regulates expression dynamics of a large gene–gene interaction system which primarily regulates immune modulatory processes modulating MS activity. The vitamin D response element was significantly enriched in this system, indicating a direct regulation of this gene interaction network through the vitamin D receptor. With increasing 25(OH)D levels, resulting regulation of this system was associated with a decrease in MS activity. Within the complex network of genes that are regulated by 25(OH)D, well-described targets of IFNB-1b and a regulator of sphingosine-1-phosphate bioavailability were found. The 25(OH)D effects on MS activity were additively enhanced by IFNB-1b. Interpretation Here, we provide mechanistic evidence that an unbalanced 25(OH)D gene expression system may affect MS activity. Our findings support a potential benefit of monitoring and managing vitamin D levels (e.g., through supplementation) in early MS patients treated with IFN-beta-1b

Weighing Evidence from Mendelian Randomization—Early-Life Obesity as a Causal Factor in Multiple Sclerosis?

In this Perspective, Alberto Ascherio and Kassandra Munger discuss the implications of Richards and colleagues' study exploring the role of early-life obesity in risk of multiple sclerosis

Animal exposure over the life-course and risk of multiple sclerosis: A case-control study within two cohorts of US women

Background: Whether animal exposure and specifically the timing of such exposure alters multiple sclerosis (MS) risk is unclear. We examined whether animal exposure was associated with MS risk, and whether risk differed by the participants age.Methods: We conducted a case-control study within the Nurses' Health Study ((NHS)/NHSII cohorts). Overall, 151 women with MS and 235 controls, matched by age and study cohort, completed an animal exposure history questionnaire. Animal exposure pre-MS onset was assessed as 'any' exposure, then by the participants age, and animal family. Conditional logistic regression was used to estimate relative MS risks, adjusted (adj.RR) for potential confounders.Results: 'Any' animal exposure was reported by 136 (90.1%) MS cases compared to 200 (85.1%) matched controls, with dog exposure being the most common [120 (79.5%) cases vs. 170 (72.3%) controls]. There was no association between 'any' animal exposure and MS risk (adj.RR:1.52;95%CI:0.76-3.04). However, both 'any' animal and specifically dog exposure at ages 10-14 years were associated with an increased MS risk (adj.RR:1.67;95%CI:1.05-2.66 and 1.76;95%CI:1.12-2.78, respectively).Conclusion: Animal exposure, and specifically dog exposure, in early adolescence was associated with an increased risk of MS. Further work is needed to confirm this finding.</p