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

Efficacy and safety outcomes in vitamin D supplement users in the fingolimod phase 3 trials

BACKGROUND:Low serum levels of 25-hydroxyvitamin D have been associated with worse outcomes in multiple sclerosis (MS) patients treated with interferon-beta. Association of vitamin D nutrition on the outcomes of other MS therapies has been studied less.OBJECTIVE:Whether patients in the phase 3 fingolimod trials using vitamin D supplements have better clinical, MRI and safety outcomes than non-users.MATERIALS AND METHODS:Pooled data from phase 3 FREEDOMS trials was analyzed post hoc. Vitamin D use was defined as 'non-users' (n = 562), 'casual users' (n = 157) and 'daily users' (usage 100% time in the study, n = 110).RESULTS:Expanded Disability Status Scale change from baseline to month 24, and annual relapse rate and proportion of patients with relapses were similar across the vitamin D user groups. Proportion of patients free of new/enlarging T2 lesions significantly favored vitamin D 'daily users' versus 'non-users'. Mean number of lesions were lower and proportion of patients free of gadolinium-enhanced T1-lesions were higher in the 'daily users'. At month 12, percent brain volume change was significantly lower in the 'daily users' versus 'non-users' and remained low at month 24 (non-significant). Incidence of depression was lower for vitamin D 'daily users' (non-significant).CONCLUSIONS:We observed improved MRI outcomes on percent brain volume change and proportion of patients free of new/enlarging T2 lesions, and a trend of less depression in the 'daily users' of vitamin D supplement in patients in the FREEDOMS trials.</p

Epstein–Barr virus and multiple sclerosis risk in the Finnish Maternity Cohort

Abstract Objective: To determine whether maternal Epstein–Barr virus (EBV) IgG antibody levels are associated with risk of multiple sclerosis (MS) in the offspring. Methods: We conducted a prospective nested case–control study in the Finnish Maternity Cohort (FMC) with serum samples from &gt;800,000 women collected during pregnancy since 1983. Cases of MS among offspring born between 1983 and 1991 were identified via hospital and prescription registries; 176 cases were matched to up to 3 controls (n = 326) on region and dates of birth, sample collection, and mother‘s birth. We used conditional logistic regression to estimate relative risks (RRs) and adjusted models for sex of the child, gestational age at sample collection, and maternal serum 25‐hydroxyvitamin D and cotinine levels. Similar analyses were conducted among 1,049 women with MS and 1,867 matched controls in the FMC. Results: Maternal viral capsid antigen IgG levels during pregnancy were associated with an increased MS risk among offspring (RRtop vs bottom quintile = 2.44, 95% confidence interval [CI] = 1.20–5.00, p trend = 0.004); no associations were found between maternal EBV nuclear antigen 1 (EBNA‐1), diffuse early antigen, or cytomegalovirus IgG levels and offspring MS risk. Among women in the FMC, those in the highest versus lowest quintile of EBNA‐1 IgG levels had a 3‐fold higher risk of MS (RR = 3.21, 95% CI = 2.37–4.35, p trend &lt;1.11e‐16). These associations were not confounded or modified by 25‐hydroxyvitamin D. Interpretation: Offspring of mothers with high viral capsid antigen IgG during pregnancy appear to have an increased risk of MS. The increase in MS risk among women with elevated prediagnostic EBNA‐1 IgG levels is consistent with previous results