Neonatal Vitamin D Levels Linked to Future MS Risk

December 01, 2016

A new study has shown a link between low levels of vitamin D in neonates and future risk for multiple sclerosis (MS), which the authors say strengthens the justification for routine vitamin D supplementation in pregnancy.

The Danish case control study, published online in Neurology on November 30, found an inverse association between neonatal levels of 25-hydroxyvitamin D (25[OH]D) and risk for MS as a young adult.

The authors, led by Nete Munk Nielsen, MD, Statens Serum Institut, Copenhagen, Denmark, say that their results, together with the high global prevalence of low vitamin D levels among pregnant women, and the fact that increasing maternal vitamin D levels is likely to reduce the mother's risk for MS as well as her offspring's, provides a rationale for universal vitamin D supplementation in pregnancy.

"Our study was conducted in Denmark, where vitamin D levels tend to be substantially lower than in the US, so we cannot generalize to the US population," senior author, Alberto Ascherio, MD, Harvard Medical School, Boston, Massachusetts, commented to Medscape Medical News. "Even in the US, however, most experts do recommend vitamin D supplements in pregnancy because the overall benefits are thought to outweigh the minimal risk (usually from accidental overdosage)."

"Keep Maternal 25(OH)D Levels > 50 nmol/L"

He added: "Although we did not measure maternal 25(OH)D directly in this study, newborn vitamin D levels are correlated and often lower than maternal levels, so at a minimum it is important to keep maternal blood levels of 25(OH)D > 50 nmol/L (>20 ng/dL). These levels could be achieved with changes in lifestyle, but supplements do help."

Accompanying the publication in Neurology is an editorial by Ruth Ann Marrie, MD, departments of Internal Medicine and Community Health Services, University of Manitoba, Winnipeg, Canada, and Martin Daumer, PhD, Sylvia Lawry Centre for Multiple Sclerosis Research eV–The Human Motion Institute, Munich, Germany.

"Although we do not know the precise target level of 25(OH)D that would be adequate to prevent MS in most individuals, or the precise period when adequate exposure to 25(OH)D is needed, we can still aim to ensure that pregnant women and their offspring achieve the minimum levels of 25(OH)D that are considered important for health (i.e., >50 nmol/L) lifelong, and are nontoxic," they write.

For the study, dried blood spots samples belonging to 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, 1 or 2 controls with the same sex and birth date were retrieved from the Biobank. The levels of 25(OH)D in the blood samples were measured by using liquid chromatography-tandem mass spectroscopy.

Result showed that lower levels of 25(OH)D in neonates were associated with an increased risk for MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile (<20.7 nmol/L) and lowest among those in the top quintile (≥48.9 nmol/L) of 25(OH)D, with an odds ratio (OR) for top vs bottom of 0.53 (95% confidence interval [CI], 0.36 - 0.78).

In the analysis treating 25(OH)D as a continuous variable, a 25-nmol/L increase in neonatal 25(OH)D resulted in a 30% reduced risk for MS (OR, 0.70; 95% CI, 0.57 - 0.84).

They note that most previous studies have examined the relevance of vitamin D intake, ultraviolet radiation, or serum 25(OH)D levels in adolescence or adulthood to MS risk; few studies have examined the possible association between in utero vitamin D levels and risk for MS. The findings have been conflicting.

Furthermore, direct measurements of in utero levels of D vitamin are not possible, so any association has been addressed by using different markers of fetal vitamin D levels, including maternal intake of vitamin D during pregnancy, maternal serum levels of 25(OH)D during pregnancy, or — as in this study — neonatal levels of vitamin D.

The authors also point out that individuals participating in the present study were young (the majority born after 1981), and many had not yet reached the age of peak MS incidence by the time of the study (2012). "Thus our findings largely reflect the association between neonatal vitamin D levels and MS diagnosis up to age 30, and may not necessary be applicable to MS onset in older individuals."

But they conclude that: "Nevertheless, our results support previous suggestions of a protective role for vitamin D in the development of MS."

Screening vs Universal Supplementation?

Dr Ascherio said there was no convincing data on whether screening for levels of 25(OH)D is needed or whether universal supplementation is more cost-effective. Moreover, there is no consensus on the optimum dose that might be given if supplementation is recommended.

"Our study does not directly determine optimal dose, which depends on exposure to sunlight, diet and body weight.  Most recommendations range from 600 IU/d to 4,000 IU/d of oral vitamin D3.  Further, vitamin D levels in childhood and adolescence are at least equally important and probably more important for MS prevention than levels at birth, so adequate vitamin D levels through diet, judicious sunlight exposure, or supplements should be continued throughout childhood and early adult life."

In terms of optimal levels of 25(OH)D, again there is no definite consensus but "overall evidence from non-pregnant adult studies suggests that the lowest MS risk is observed at levels of 100 to 115 nmol/L (40 to 45 ng/dL). These are the levels observed in healthy young adults with sufficient sunlight exposure."

In their editorial, Dr Marrie and Dr Daumer point out that the results are consistent with those from another recent case-control study in the Finnish Maternity Cohort, which they say is "reassuring." In that study, each 50-nmol/L increase in 25(OH)D was associated with a 24% reduced risk for MS.

On the issue of screening vs universal supplementation, Dr Marrie added: "Given that we have little direct evidence about the influence of supplementation, and that individual responses to supplementation differ based on a variety of factors, I would not recommend a specific dose for vitamin D supplementation.

"Instead, I would favor defining a target 25(OH)D level, and using supplementation to achieve that level. As to the optimal target, this is still unclear but it would be reasonable to target a level of greater than 50 nmol/L. This is the level recommended by the Institute of Medicine for general health and is safe. Based on the findings by Nielsen et al. this should achieve an important reduction in MS risk. Future studies can address the optimal target level."

The study was supported by the Danish Society of Multiple Sclerosis and the Aase & Ejnar Danielsen's Foundation. Dr Ascherio and Dr Munger are supported by research grants from the National Institutes of Health and National Multiple Sclerosis Society for the investigation of the role of vitamin D and other risk factors in MS. The authors have disclosed no relevant financial relationships.

Neurology. Published online November 30. Abstract, Editorial

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