Table 1. Characteristics of population studies investigating influence of vitamin D availability in early life and the risk of MS in adulthood.
| First author, y (ref) | Objective | Study design | Study setting | Exposure | Median/Mean age at MS onset | Gender distribution of cases n (%) | Population | Main findings | Quality | |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | Male | |||||||||
| Mirzaei et al. 2011 [28] | To study the effect of gestational vitamin D on adult onset of MS | Cohort | USA | Dietary vitamin D Fortified milk Predicted serum 25(OH)D | n.a | Female nurses 35,372 |
n = 35,794 mothers of participants, n = 199 MS cases | High maternal milk (RR 0.62, 95%CI 0.40–0.95), vitamin D intake (RR 0.57, 95% CI 0.35–0.91) and serum (25(OH)D) level (RR 0.59, 95% CI 0.37–0.92) associated with lower risk of developing MS in offspring | 8 | |
| Salzer et al. 2012 [23] | To examine the association between 25-hydroxyvitamin D levels and the risk of MS in blood samples collected prospectively and during gestation | Prospective nested case—control | Sweden | 25(OH)D levels during early pregnancy | Median 21 (13–32) | 27 (73) | 10 (27) | n = 37 cases, n = 185 controls | MS risk in offspring exposed to low gestational 25(OH)D levels (<75 nmol/L vs. ≥75 nmol/L) not different (OR 1.8, 95% CI 0.53–5.8) | 6 |
| Ueda et al. 2014 [24] | To assess the relation between neonatal vitamin D concentration, measured in stored blood samples, and risk of MS | Population based case—control | Sweden | 25(OH)D levels in newborns | Mean 25.1 [4.7] | 349 (76) | 110 (24) | n = 459 cases, n = 663 controls | No association between neonatal 25 -hydroxyvitamin D quintile and risk of MS (OR 1.0, 95% CI 0.68–1.44) | 8 |
| Cortese et al. 2015 [27] | To investigate the association between vitamin D3 supplementation at different postnatal ages and MS risk | Case—control | Norway | Cod liver oil supplements | Mean 37.6 [10.2] | 667 (70) | 286 (30) | n = 953 cases, n = 1,717 controls | Supplementation during early childhood (0-12y) did not influence MS risk (OR 1.01, 95% CI 0.81–1.26) | 6 |
| Munger et al. 2016 [25] | To examine whether serum 25-hydroxyvitamin D levels in early pregnancy are associated with risk of MS in offspring | Prospective nested case—control | Finland | Maternal serum 25(OH)D levels | Mean 19.8 [3.2] | 163 (84) | 30 (16) | n = 176 cases, n = 326 controls | Maternal vitamin D deficiency (25(OH)D levels, 12.02 ng/ml) during early pregnancy was associated with nearly two fold higher risk of MS in the offspring (RR 1.90, 95% CI 1.20–3.01) | 8 |
| Nielsen et al. 2017 [26] | To examine direct association between level of neonatal vitamin D and risk of MS | Population based case—control | Denmark | 25(OH)D levels in newborns | n.a | 354 (68) | 167 (32) | n = 521 cases, n = 972 controls | In the quantile based analysis, MS risk was highest among individuals in the lowest quintile (<20.7nmol/L vs ≥48.9 nmol/L) (OR 0.53, 95% CI 0.36–0.78). In the analysis of 25(OH)D as a continuous variable, a 25nmol/L increase reduced the risk of MS by 30% (OR 0.70, 95% CI 0.57–0.84) | 8 |
MS, multiple sclerosis; n.a, not available; RR, relative risk; CI, confidence interval; OR, odds ratio; [SD], standard deviation/(range).