Low Vitamin D in Pregnancy Linked to Higher MS in Offspring

March 17, 2016

Children of mothers with vitamin D deficiency during early pregnancy had an increased risk of developing multiple sclerosis (MS) in adulthood, in a new study.

The study, published online in JAMA Neurology on March 7, was conducted by a team led by Kassandra L. Munger, ScD, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

"This result supports a role of prenatal vitamin D in determining multiple sclerosis risk and suggests that correction of vitamin D deficiency during pregnancy may reduce the risk of MS in the offspring,” the researchers conclude.

"We cannot say this is a causal link, although one explanation could be that it is causal,” Dr Munger commented to Medscape Medical News. "Our results do however suggest that vitamin D levels early in life may be important for future risk of MS."

"This is not enough evidence to recommend vitamin D supplementation routinely in pregnancy specifically to reduce MS risk. It is premature to make such a jump. But pregnant women might want to talk to their doctors about vitamin D status — it is another reason to think about doing this," she added.

The study was made possible by using the Finnish Maternity Cohort, established in 1983 and composed of more than 800,000 women and more than 1.5 million serum samples collected during early pregnancy and stored at –25°C.

For the current case-control study, the researchers identified 193 individuals with a diagnosis of MS whose mothers were in the Finnish Maternity Cohort. Of these, 176 (cases) were matched 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.

Results showed that the mean maternal vitamin D levels were in the insufficient range but somewhat higher in maternal control than case samples (15.02 ng/mL vs 13.86 ng/mL).

"While average vitamin D levels were not vastly different between the two groups, mothers of those who went on to develop MS were much more likely to be vitamin D deficient," Dr Munger said.

Maternal vitamin D deficiency — defined as 25(OH)D levels below 12.02 ng/mL — during early pregnancy was associated with a nearly 2-fold increased risk for MS in the offspring compared with women who did not have deficient 25(OH)D levels (relative risk, 1.90; 95% confidence interval, 1.20 - 3.01; P = .006).

While the range of maternal 25(OH)D spanned levels of deficient to sufficiency, most women in the study had deficient or insufficient levels (<20.03 ng/mL), and only 10 mothers had levels above 30.05 ng/mL; only 1 had levels above 40.06 ng/mL.

"Thus, while our results suggest that vitamin D deficiency during pregnancy increases MS risk in the offspring, our study does not provide any information as to whether there is a dose-response effect with increasing levels of 25(OH)D sufficiency," the researchers say. They add that similar studies in populations with a wider distribution of 25(OH)D are needed for this.

Dr Munger noted that two previous studies have not found any association between pregnancy/neonatal vitamin D levels and future MS risk. "But both these studies had limitations, including small sample sizes and less reliable controls. Our study has some strengths that these previous studies lacked," she said.

The researchers also point out that a study of gestational dietary vitamin D intake in US women found that higher intake was associated with a decreased risk for MS in the child. Additionally, it has been suggested that the higher number of spring births observed among patients with MS may be due to less vitamin D exposure in utero.

Dr Munger said the current results ideally needed to be replicated in other populations."But that is a very difficult thing to do unless maternal blood samples have been stored as in Finland."

She noted that Finland is unusual in that it stores such blood samples and also keeps universal health records. "The Finnish maternal cohort was not designed for research but it has become an invaluable research database," she added.

"We would like to follow the cohort further and repeat this study when the offspring are older and more cases of MS may have occurred," she commented.

In an accompanying editorial, Benjamin M. Greenberg, MD, University of Texas Southwestern, Dallas, points out that there are two theoretical connections between vitamin D deficiency and the pathogenesis of MS.

He notes that activation of the vitamin leads to suppression of proinflammatory T-cell populations in MS models, and vitamin D pathways have also been implicated in myelin formation.

"The potential correlation between in utero vitamin D deficiency and MS would have both basic science and clinical implications," he says.

This study was funded by grants from the National Institute of Neurological Disorders and Stroke and the National Multiple Sclerosis Society. Dr Munger has disclosed no relevant financial relationships; disclosures of coauthors appear in the paper. Dr Greenberg receives grant support from Chugai, Medimmune, and Acorda Therapeutics and consulting fees from Novartis and EMD Serono.

JAMA Neurol. Published online March 7, 2016. Full text Editorial

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