Association Between Sun Exposure and Risk of Relapse in Pediatric-Onset Multiple Sclerosis

Overview

Journal Neurol Neuroimmunol Neuroinflamm

Specialty Neurology

Date 2025 Feb 12

PMID 39938013

Authors

Gina Chang

Prince Sebastian

Akash Virupakshaiah

Vinicius A Schoeps

Nicolas Cherbuin

T Charles Casper

Mark P Gorman

Leslie A Benson

Tanuja Chitnis

Mary Rensel

Aaron W Abrams

Tim Lotze

Soe S Mar

Teri L Schreiner

Yolanda S Wheeler

John W Rose

Jennifer Graves

Lauren B Krupp

Amy T Waldman

Robyn Lucas

Emmanuelle Waubant

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Low sun and ultraviolet radiation (UVR) exposures have been associated with increased risk of developing pediatric-onset multiple sclerosis (MS); however, their effect on disease course has not been well characterized. We primarily investigated whether there was an association between time spent in the sun in early childhood and risk of relapse in pediatric MS. We secondarily investigated the effect of sun exposure during more recent periods on risk of relapse.

Methods: We conducted a multicenter cohort study of participants with pediatric-onset MS recruited from 18 pediatric MS clinics across the United States between November 1, 2011, and July 1, 2017. Relapses were identified prospectively after study enrollment; relapses preceding study enrollment were entered retrospectively. Time spent in the sun at various periods of life was measured using a detailed environmental questionnaire, and ambient UVR exposure was determined using zip codes. Multivariable Cox regression models were used to assess the association between time spent in the sun and UVR dose at specific periods of life and the risk of relapse. Models were adjusted for demographic, clinical, and sun exposure-related characteristics.

Results: In our cohort of 334 children with MS, 206 (62%) experienced at least one relapse from disease onset to the end of the follow-up period. After adjustment, ≥30 minutes of daily sun exposure during the first summer of life was associated with a lower risk of relapse compared with <30 minutes (adjusted hazard ratio [aHR] 0.67, CI 0.48-0.92, = 0.01). Greater time spent in the sun during the second trimester of pregnancy was also associated with reduced risk of relapse (aHR 0.68, CI 0.48-0.97, = 0.04). UVR dose and time spent in the sun later in life were not significantly associated with relapse risk.

Discussion: In this large cohort study of children with MS, greater early childhood and prenatal sun exposure time was associated with lower risk of relapse. Further investigation of sun exposure at other periods is needed to better characterize its impact on disease course and guide potential future interventions.

References

Banwell B, Bar-Or A, Arnold D, Sadovnick D, Narayanan S, McGowan M . Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol. 2011; 10(5):436-45. DOI: 10.1016/S1474-4422(11)70045-X. View

Lucas R, Ponsonby A, Dear K, Valery P, Pender M, Taylor B . Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology. 2011; 76(6):540-8. DOI: 10.1212/WNL.0b013e31820af93d. View

Lavery A, Collins B, Waldman A, Hart C, Bar-Or A, Marrie R . The contribution of secondhand tobacco smoke exposure to pediatric multiple sclerosis risk. Mult Scler. 2018; 25(4):515-522. DOI: 10.1177/1352458518757089. View

Polman C, Reingold S, Banwell B, Clanet M, Cohen J, Filippi M . Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011; 69(2):292-302. PMC: 3084507. DOI: 10.1002/ana.22366. View

Smith S, Li J, Garbett K, Mirnics K, Patterson P . Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007; 27(40):10695-702. PMC: 2387067. DOI: 10.1523/JNEUROSCI.2178-07.2007. View

Simpson Jr S, Taylor B, Blizzard L, Ponsonby A, Pittas F, Tremlett H . Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010; 68(2):193-203. DOI: 10.1002/ana.22043. View

Tremlett H, Devonshire V . Does the season or month of birth influence disease progression in multiple sclerosis?. Neuroepidemiology. 2006; 26(4):195-8. DOI: 10.1159/000092406. View

Gorman M, Healy B, Polgar-Turcsanyi M, Chitnis T . Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol. 2009; 66(1):54-9. DOI: 10.1001/archneurol.2008.505. View

van der Mei I, Ponsonby A, Dwyer T, Blizzard L, Simmons R, Taylor B . Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ. 2003; 327(7410):316. PMC: 169645. DOI: 10.1136/bmj.327.7410.316. View

10.

Staples J, Ponsonby A, Lim L . Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis. BMJ. 2010; 340:c1640. PMC: 2862149. DOI: 10.1136/bmj.c1640. View

11.

Hempel S, Graham G, Fu N, Estrada E, Chen A, Miake-Lye I . A systematic review of modifiable risk factors in the progression of multiple sclerosis. Mult Scler. 2017; 23(4):525-533. DOI: 10.1177/1352458517690270. View

12.

Hart P, Gorman S . Exposure to UV Wavelengths in Sunlight Suppresses Immunity. To What Extent is UV-induced Vitamin D3 the Mediator Responsible?. Clin Biochem Rev. 2013; 34(1):3-13. PMC: 3626364. View

13.

Milliken S, Wassall H, Lewis B, Logie J, Barker R, Macdonald H . Effects of ultraviolet light on human serum 25-hydroxyvitamin D and systemic immune function. J Allergy Clin Immunol. 2012; 129(6):1554-61. DOI: 10.1016/j.jaci.2012.03.001. View

14.

Wright C, Wilkes M, du Plessis J, Reeder A . Self-reported skin colour and erythemal sensitivity vs. objectively measured constitutive skin colour in an African population with predominantly dark skin. Photodermatol Photoimmunol Photomed. 2015; 31(6):315-24. DOI: 10.1111/phpp.12191. View

15.

Correale J, Ysrraelit M, Gaitan M . Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain. 2009; 132(Pt 5):1146-60. DOI: 10.1093/brain/awp033. View

16.

Sebastian P, Cherbuin N, Barcellos L, Roalstad S, Casper C, Hart J . Association Between Time Spent Outdoors and Risk of Multiple Sclerosis. Neurology. 2021; 98(3):e267-e278. PMC: 8792813. DOI: 10.1212/WNL.0000000000013045. View

17.

Hauser S, Cree B . Treatment of Multiple Sclerosis: A Review. Am J Med. 2020; 133(12):1380-1390.e2. PMC: 7704606. DOI: 10.1016/j.amjmed.2020.05.049. View

18.

Hart P, Lucas R, Booth D, Carroll W, Nolan D, Cole J . Narrowband UVB Phototherapy for Clinically Isolated Syndrome: A Trial to Deliver the Benefits of Vitamin D and Other UVB-Induced Molecules. Front Immunol. 2017; 8:3. PMC: 5256075. DOI: 10.3389/fimmu.2017.00003. View

19.

Cassard S, Fitzgerald K, Qian P, Emrich S, Azevedo C, Goodman A . High-dose vitamin D supplementation in relapsing-remitting multiple sclerosis: a randomised clinical trial. EClinicalMedicine. 2023; 59:101957. PMC: 10130605. DOI: 10.1016/j.eclinm.2023.101957. View

20.

Tremlett H, Zhu F, Ascherio A, Munger K . Sun exposure over the life course and associations with multiple sclerosis. Neurology. 2018; 90(14):e1191-e1199. PMC: 5890609. DOI: 10.1212/WNL.0000000000005257. View