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

TY - JOUR

T1 - Infections seem to be more frequent before onset of pediatric multiple sclerosis

T2 - A Danish nationwide nested case-control study

AU - Boesen, Magnus Spangsberg

AU - Koch-Henriksen, Nils

AU - Thygesen, Lau Caspar

AU - Eriksson, Frank

AU - Greisen, Gorm

AU - Born, Alfred Peter

AU - Blinkenberg, Morten

AU - Uldall, Peter Vilhelm

AU - Magyari, Melinda

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - association

KW - childhood

KW - infection

KW - MS

KW - pediatric

KW - risk

U2 - 10.1177/1352458518771871

DO - 10.1177/1352458518771871

M3 - Journal article

C2 - 29770725

SN - 1352-4585

VL - 25

SP - 783

EP - 791

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

IS - 2

ER -