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Infections seem to be more frequent before onset of pediatric multiple sclerosis: A Danish nationwide nested
Magnus Spangsberg Boesen1, Nils Koch-Henriksen2, Lau Caspar Thygesen3
1Department of Paediatrics, Juliane Marie Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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.
Insights
Childhood infections may increase the risk of pediatric multiple sclerosis (MS). Studies show that each infection in the preceding three years elevates MS hazard, with five or more infections doubling the risk.
Area of Science:
- Pediatric Neurology
- Infectious Disease Epidemiology
- Autoimmune Disease Research
Background:
- Infections are potential environmental triggers for multiple sclerosis (MS).
- The link between childhood infections and pediatric MS risk remains uninvestigated.
Purpose of the Study:
- To determine if childhood infections contribute to the development of pediatric MS.
- To analyze the relationship between the cumulative number of infections and pediatric MS risk.
Main Methods:
- A nationwide nested case-control study in Denmark.
- Matched 212 pediatric MS cases with 1,060 controls.
- Used Cox regression to estimate hazard ratios for MS based on cumulative childhood infections.
Main Results:
- Each infection in the 3 years prior to MS onset increased MS hazard by 11%.
- Children with 5+ infections in the preceding 3 years had double the hazard of developing MS.
- The median age of MS onset was 15.3 years, with 72% of cases being girls.
Conclusions:
- Pediatric MS cases reported more infections in the 3 years before clinical onset.
- Immune responses to infections may play a role in the pathogenesis of MS.
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