Sage Journals: Discover world-class research

Abstract

Background:

Infections are suspected environmental triggers for multiple sclerosis (MS). The relationship between the timing and cumulative number of childhood infections regarding pediatric MS risk is uninvestigated.

Objectives:

To investigate whether childhood infections contribute to pediatric MS.

Methods:

A nationwide nested case–control study with detailed MS case ascertainment including chart review was undertaken. For each MS case, we selected five control children using density sampling from the entire Danish population, matching controls to children with MS by sex and birthdate. We analyzed data with the cumulative number of childhood infections as exposure and MS as outcome. Hazard ratios (HRs) including 95% confidence intervals (CIs) were estimated using Cox regression.

Results:

We identified 212 children with MS and 1,060 controls. Median age at MS onset was 15.3 years (range: 7.6–17.8 years); 72% were girls. Each infection during the preceding 3 years increased the hazard for MS by 11% (95% CI = 1.01–1.22, p = 0.04); having 5+ infections compared with 0–4 infections in the preceding 3 years doubled the hazard for MS (HR: 2.18; 95% CI = 1.12–4.30, p = 0.02).

Conclusion:

Children with MS appeared to have more infections in the 3 years preceding MS clinical onset; accordingly, immune response to infections may influence MS pathogenesis.

Keywords

MS pediatric risk association infection childhood

Get full access to this article

View all access options for this article.

References

Chitnis

. Role of puberty in multiple sclerosis risk and course. Clin Immunol 2013; 149(2): 192–200.

Ascherio

Munger

Lünemann

. The initiation and prevention of multiple sclerosis. Nat Rev Neurol 2012; 8(11): 602–612.

Boesen

Magyari

Koch-Henriksen

et al . Pediatric-onset multiple sclerosis and other acquired demyelinating syndromes of the central nervous system in Denmark during1977–2015: A nationwide population-based incidence study. Mult Scler 2018; 24: 1077–1086.

Statens Serum Institut. Overvågning i tal, grafer og kort, https://www.ssi.dk/data (accessed 3 January 2018).

McLeod

Hammond

Kurtzke

. Migration and multiple sclerosis in immigrants to Australia from United Kingdom and Ireland: A reassessment. I. Risk of MS by age at immigration. J Neurol 2011; 258(6): 1140–1149.

Gale

Martyn

. Migrant studies in multiple sclerosis. Prog Neurobiol 1995; 47(4–5): 425–448.

Pohl

Krone

Rostasy

et al . High seroprevalence of Epstein-Barr virus in children with multiple sclerosis. Neurology 2006; 67(11): 2063–2065.

Alotaibi

Kennedy

Tellier

et al . Epstein-Barr virus in pediatric multiple sclerosis. JAMA 2004; 291(15): 1875–1879.

Thacker

Mirzaei

Ascherio

. Infectious mononucleosis and risk for multiple sclerosis: A meta-analysis. Ann Neurol 2006; 59(3): 499–503.

10.

Nørgaard

Nielsen

Jacobsen

et al . Use of penicillin and other antibiotics and risk of multiple sclerosis: A population-based case-control study. Am J Epidemiol 2011; 174(8): 945–948.

11.

Alonso

Jick

et al . Antibiotic use and risk of multiple sclerosis. Am J Epidemiol 2006; 163(11): 997–1002.

12.

Waubant

Mowry

Krupp

et al . Common viruses associated with lower pediatric multiple sclerosis risk. Neurology 2011; 76(23): 1989–1995.

13.

Makhani

Banwell

Tellier

et al . Viral exposures and MS outcome in a prospective cohort of children with acquired demyelination. Mult Scler 2016; 22 (3): 385–388.

14.

Tremlett

Fadrosh

Faruqi

et al . Gut microbiota in early pediatric multiple sclerosis: A case-control study. Eur J Neurol 2016; 23(8): 1308–1321.

15.

Tremlett

Fadrosh

Faruqi

et al . Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls. BMC Neurol 2016; 16(1): 182.

16.

Statistikbanken, http://www.statistikbanken.dk/statbank5a/default.asp?w=1920 (accessed 31 October 2016).

17.

Thygesen

Daasnes

Thaulow

et al . Introduction to Danish (nationwide) registers on health and social issues: Structure, access, legislation, and archiving. Scand J Public Health 2011; 39 (7 Suppl.): 12–16.

18.

Koch-Henriksen

Magyari

Laursen

. Registers of multiple sclerosis in Denmark. Acta Neurol Scand Suppl 2015; 132(199): 4–10.

19.

Koch-Henriksen

Rasmussen

Stenager

et al . The Danish Multiple Sclerosis Registry. History, data collection and validity. Dan Med Bull 2001; 48(2): 91–94.

20.

Polman

Reingold

Edan

et al . Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.” Ann Neurol 2005; 58(6): 840–846.

21.

Poser

Paty

Scheinberg

et al . New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Ann Neurol 1983; 13(3): 227–231.

22.

Krupp

Tardieu

Amato

et al . International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: Revisions to the 2007 definitions. Mult Scler 2013; 19(10): 1261–1267.

23.

Pedersen

. The Danish Civil Registration System. Scand J Public Health 2011; 39(7 Suppl.): 22–25.

24.

Suissa

. Immortal time bias in observational studies of drug effects. Pharmacoepidemiol Drug Saf 2007; 16(3): 241–249.

25.

Lynge

Sandegaard

Rebolj

. The Danish National Patient Register. Scand J Public Health 2011; 39(7 Suppl.): 30–33.

26.

Pottegård

Schmidt

SAJ

Wallach-Kildemoes

et al . Data Resource Profile: The Danish National Prescription Registry. Int J Epidemiol 2016; 46: 798–798f.

27.

Andersen

Olivarius

NDF

Krasnik

. The Danish National Health Service Register. Scand J Public Health 2011; 39(7 Suppl.): 34–37.

28.

Borgan Goldstein

ØL

Langholz

. Methods for the analysis of sampled cohort data in the cox proportional hazards model. Ann Statist 1995; 23: 1749–1778.

29.

Aalen

Borgan Gjessing

ØH

. Survival and event history analysis: A process point of view. New York: Springer, 2008, pp. 190–203.

30.

Borgan

Zhang

. Using cumulative sums of martingale residuals for model checking in nested case-control studies. Biometrics 2015; 71(3): 696–703.

31.

Andersen

. Adjustment for misclassification in studies of familial aggregation of disease using routine register data. Stat Med 2002; 21(23): 3595–3607.

32.

Sibley

Bamford

Clark

. Clinical viral infections and multiple sclerosis. Lancet 1985; 1(8441): 1313–1315.

33.

Salvetti

Giovannoni

Aloisi

. Epstein-Barr virus and multiple sclerosis. Curr Opin Neurol 2009; 22(3): 201–206.

34.

Leibowitz

Antonovsky

Medalie

et al . Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation. J Neurol Neurosurg Psychiatry 1966; 29(1): 60–68.

35.

Magyari

Koch-Henriksen

Pfleger

et al . Physical and social environment and the risk of multiple sclerosis. Mult Scler Relat Disord 2014; 3(5): 600–606.

36.

Bager

Nielsen

Bihrmann

et al . Childhood infections and risk of multiple sclerosis. Brain J Neurol 2004; 127(Pt 11): 2491–2497.

37.

Bager

Nielsen

Bihrmann

et al . Sibship characteristics and risk of multiple sclerosis: A nationwide cohort study in Denmark. Am J Epidemiol 2006; 163(12): 1112–1117.

38.

Koch-Henriksen

. An epidemiological study of multiple sclerosis. Familial aggregation social determinants, and exogenic factors. Acta Neurol Scand Suppl 1989; 124: 1–123.

39.

Skolebørnsundersøgelsen 2014, http://www.hbsc.dk/rapport.php?file=HBSC-Rapport-2014.pdf (accessed 3 January 2018).

40.

Madsen

Rasmussen

Mejborn

et al . Vitamin D status and its determinants in children and adults among families in late summer in Denmark. Br J Nutr 2014; 112(5): 776–784.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.39 MB

Infections seem to be more frequent before onset of pediatric multiple sclerosis: A Danish nationwide nested case–control study

Abstract

Background:

Objectives:

Methods:

Results:

Conclusion:

Keywords

Get full access to this article

References

Supplementary Material