Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study

doi:10.1212/WNL.0000000000003454

. 2017 Jan 3;88(1):44-51.

doi: 10.1212/WNL.0000000000003454. Epub 2016 Nov 30.

Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study

Affiliations

¹ From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA. NMN@ssi.dk.
² From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

PMID: 27903815
PMCID: PMC5200855
DOI: 10.1212/WNL.0000000000003454

Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study

Nete Munk Nielsen et al. Neurology. 2017.

. 2017 Jan 3;88(1):44-51.

doi: 10.1212/WNL.0000000000003454. Epub 2016 Nov 30.

Affiliations

¹ From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA. NMN@ssi.dk.
² From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

PMID: 27903815
PMCID: PMC5200855
DOI: 10.1212/WNL.0000000000003454

Abstract

Objective: As previous research has suggested that exposure to vitamin D insufficiency in utero may have relevance for the risk of multiple sclerosis (MS), we aimed to examine the direct association between level of neonatal vitamin D and risk of MS.

Methods: We carried out a matched case-control study. Dried blood spots samples (DBSS) belonging to 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, 1-2 controls with the same sex and birth date were retrieved from the Biobank (n = 972). Level of 25-hydroxyvitamin D (25[OH]D) in the DBSS was measured using liquid chromatography tandem mass spectroscopy. The association between different levels of 25(OH)D and risk of MS was evaluated by odds ratios (OR) calculated in conditional logistic regression models.

Results: We observed that lower levels of 25(OH)D in neonates were associated with an increased risk of 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 of 25(OH)D (≥48.9 nmol/L), with an 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 of MS (OR 0.70, 95% CI 0.57-0.84).

Conclusion: Low concentrations of neonatal vitamin D are associated with an increased risk of MS. In light of the high prevalence of vitamin D insufficiency among pregnant women, our observation may have importance for public health.

PubMed Disclaimer

Figures

**Figure 1. Study flowchart**
Flowchart shows the identification of patients with multiple sclerosis (MS) and controls.

**Figure 2. Mean levels of 25-hydroxyvitamin D (25[OH]D) according to year of birth**
Mean levels of 25(OH)D by year of birth among patients with multiple sclerosis (MS) and controls. Ninety-five percent confidence intervals are shown on the figure. *Based on very few cases: in 1994, 7 cases and 13 controls; in 1995, 4 cases and 8 controls; in 1996, 6 cases and 13 controls; and in 1997, 3 cases and 6 controls. One case and 2 controls were born in 2000 (not shown).

**Figure 3. Mean levels of 25-hydroxyvitamin D (25[OH]D) according to month of birth**
Mean levels of 25(OH)D by month of birth among patients with multiple sclerosis (MS) and controls. Ninety-five percent confidence intervals are shown on the figure.

See this image and copyright information in PMC

Comment in

A gestational dose of vitamin D per day keeps the MS doctor away.
Marrie RA, Daumer M. Marrie RA, et al. Neurology. 2017 Jan 3;88(1):13-14. doi: 10.1212/WNL.0000000000003469. Epub 2016 Nov 30. Neurology. 2017. PMID: 27903816 No abstract available.
Letter re: Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study.
Zarghami A. Zarghami A. Neurology. 2017 Jul 25;89(4):410. doi: 10.1212/WNL.0000000000004138. Neurology. 2017. PMID: 28739664 No abstract available.
Letter re: Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study.
Xia Z, Cheng Q, Li J. Xia Z, et al. Neurology. 2017 Jul 25;89(4):410-411. doi: 10.1212/WNL.0000000000004139. Neurology. 2017. PMID: 28739665 No abstract available.
Author response: Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study.
Nielsen NM, Munger KL, Stenager E, Ascherio A. Nielsen NM, et al. Neurology. 2017 Jul 25;89(4):411. doi: 10.1212/WNL.0000000000004140. Neurology. 2017. PMID: 28739666 No abstract available.

Cited by

Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.
Butzkueven H, Ponsonby AL, Stein MS, Lucas RM, Mason D, Broadley S, Kilpatrick T, Lechner-Scott J, Barnett M, Carroll W, Mitchell P, Hardy TA, Macdonell R, McCombe P, Lee A, Kalincik T, van der Walt A, Lynch C, Abernethy D, Willoughby E, Barkhof F, MacManus D, Clarke M, Andrew J, Morahan J, Zhu C, Dear K, Taylor BV; PREVANZ Investigators. Butzkueven H, et al. Brain. 2024 Apr 4;147(4):1206-1215. doi: 10.1093/brain/awad409. Brain. 2024. PMID: 38085047 Free PMC article. Clinical Trial.
Risk factors for multiple sclerosis in the context of Epstein-Barr virus infection.
Hedström AK. Hedström AK. Front Immunol. 2023 Jul 24;14:1212676. doi: 10.3389/fimmu.2023.1212676. eCollection 2023. Front Immunol. 2023. PMID: 37554326 Free PMC article. Review.
Environmental Influences on Risk and Disease Course in Pediatric Multiple Sclerosis.
Dinov D, Brenton JN. Dinov D, et al. Semin Pediatr Neurol. 2023 Jul;46:101049. doi: 10.1016/j.spen.2023.101049. Epub 2023 Apr 25. Semin Pediatr Neurol. 2023. PMID: 37451747 Free PMC article.
The Role of Vitamin D in Neuroprotection in Multiple Sclerosis: An Update.
Sangha A, Quon M, Pfeffer G, Orton SM. Sangha A, et al. Nutrients. 2023 Jun 30;15(13):2978. doi: 10.3390/nu15132978. Nutrients. 2023. PMID: 37447304 Free PMC article. Review.
Emerging imaging and liquid biomarkers in multiple sclerosis.
Gill AJ, Schorr EM, Gadani SP, Calabresi PA. Gill AJ, et al. Eur J Immunol. 2023 Aug;53(8):e2250228. doi: 10.1002/eji.202250228. Epub 2023 May 28. Eur J Immunol. 2023. PMID: 37194443 Free PMC article. Review.

See all "Cited by" articles

References

1. Word Health Organization. Neurological Disorders: Public Health Challenges. Geneva: Word Health Organization; 2006:85–95.
1. Koch-Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 2010;9:520–532. - PubMed
1. Salzer J, Hallmans G, Nystrom M, Stenlund H, Wadell G, Sundstrom P. Vitamin D as a protective factor in multiple sclerosis. Neurology 2012;79:2140–2145. - PubMed
1. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296:2832–2838. - PubMed
1. Munger KL, Zhang SM, O'Reilly E, et al. . Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62:60–65. - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

[1] Word Health Organization. Neurological Disorders: Public Health Challenges. Geneva: Word Health Organization; 2006:85–95.

[2] Word Health Organization. Neurological Disorders: Public Health Challenges. Geneva: Word Health Organization; 2006:85–95.

[3] Koch-Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 2010;9:520–532. - PubMed

[4] Koch-Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 2010;9:520–532. - PubMed

[5] Salzer J, Hallmans G, Nystrom M, Stenlund H, Wadell G, Sundstrom P. Vitamin D as a protective factor in multiple sclerosis. Neurology 2012;79:2140–2145. - PubMed

[6] Salzer J, Hallmans G, Nystrom M, Stenlund H, Wadell G, Sundstrom P. Vitamin D as a protective factor in multiple sclerosis. Neurology 2012;79:2140–2145. - PubMed

[7] Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296:2832–2838. - PubMed

[8] Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296:2832–2838. - PubMed

[9] Munger KL, Zhang SM, O'Reilly E, et al. . Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62:60–65. - PubMed

[10] Munger KL, Zhang SM, O'Reilly E, et al. . Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62:60–65. - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study

Affiliations

Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study

Authors

Affiliations

Abstract

Figures

Comment in

Similar articles

Cited by

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials