Risk Factors for Pediatric MS Coming into Sharper Focus

What factors put children at risk for multiple sclerosis (MS)? While much remains to be determined, research has implicated factors including:

1. Exposure to smoking. A study involving 129 children and adolescents with MS and more than 1,000 controls found that children exposed to parental smoking had more than twice the risk of developing MS before age 16 than children not exposed to parental smoking.¹ Other research examining genes also supports a role for secondhand smoke in pediatric MS.², ³

2. Exposure to household chemicals. A 2018 study by investigators at 16 institutions found that indirect or passive exposure to certain rat and mouse poisons or weed-control agents was associated with a doubling of risk for pediatric-onset MS.⁴ Further, exposure to certain products used to control plant and tree disease was associated with a 2.7-fold increased risk for developing MS or clinically isolated syndrome (CIS) as a child. The investigators emphasize that further studies are needed.⁴

3. Epstein-Barr virus. Past infection with the Epstein-Barr virus (EBV), which is relatively common, long has been identified as a risk factor for MS in adults.⁵ Recent research has shown a significant association between having blood work indicating a history of EBV infection and pediatric onset of MS.⁶,⁷

4. Low vitamin D status. Blood levels of a form of Vitamin D known as 25-hydroxyvitamin D, or 25(OH)D, typically are lower in both pediatric and adult MS patients than in the overall population.⁸ Experts caution that further research is needed to clarify how prenatal, perinatal, and childhood Vitamin D status affects risk for pediatric MS.⁹

5. Obesity. Case-control studies have shown an association between obesity and increased risk for MS or CIS, with one study finding increased risk for both boys and girls,¹⁰ and another reporting elevated risk in girls only.¹¹ Another study examined genetic risk scores and found evidence for a causal relationship between increased body mass index (BMI) and susceptibility to pediatric MS.¹²

6. Genetics. Investigators are examining not only specific genes and gene variants, but also the even more-complex topic of how genes interact with one another and with environmental factors.¹³, ¹⁴

Researchers are also exploring the potential impact of factors such as place of residence, age at first menstrual period, age at start of daycare, dietary intake, mother’s health during pregnancy, and more.⁹

While investigators probe these areas, clinicians urge parents of children who have MS or who may be at increased risk for MS to address those risk factors that can be modified, such as exposure to smoking and obesity. Although there is not yet strong evidence that these steps will enable a child to avoid MS or modify its course, the benefits in terms of overall well-being are clear.

References

¹ Mikaeloff Y, Caridade G, Tardieu M, Suissa S; KIDSEP study group. Parental smoking at home and the risk of childhood-onset multiple sclerosis in children. Brain. 2007;130:2589-2595.
² Lavery AM, Collins BN, Waldman AT, et al. The contribution of secondhand tobacco smoke exposure to pediatric multiple sclerosis risk. Mult Scler. 2019;25(4):515-522.
³ Interactions of secondhand tobacco exposure and HLA-DRB1*15 increases the odds of pediatric multiple sclerosis. Lavery A, Collins BN, Waldman A, et al. Poster P829. ECTRIMS 32nd Annual Congress. London, United Kingdom. September 14-17, 2016.
⁴ Mar S, Liang S, Waltz M, et al. Several household chemical exposures are associated with pediatric-onset multiple sclerosis. Ann Clin Transl Neurol. 2018 Oct 9;5(12):1513-1521.
⁵ Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother. 2013;13(12 Suppl):3-9.
⁶ Waubant E, Mowry EM, Krupp L, et al. Common viruses associated with lower pediatric multiple sclerosis risk. Neurology. 2011;76:1989-1995.
⁷ Nourbakhsh B, Rutatangwa A, Waltz M, et al. Heterogeneity in association of remote herpesvirus infections and pediatric MS. Ann Clin Transl Neurol. 2018;5(10):1222-1228.
⁸ Duan S, Lv Z, Fan X, et al. Vitamin D status and the risk of multiple sclerosis: a systematic review and meta-analysis. Neurosci Lett. 2014;570:108-113.
⁹ Waubant E, Ponsonby A-L, Pugliatti M, et al. Environmental and genetic factors in pediatric inflammatory demyelinating diseases. Neurology. 2016;87(Suppl 2):S20-S27.
¹⁰ Chitnis T, Graves J, Weinstock-Guttman B, et al; US Network of Pediatric Multiple Sclerosis Centers. Distinct effects of obesity and puberty on risk and age at onset of pediatric MS. Poster. ECTRIMS 31st Annual Congress. Barcelona, Spain. October 7–10, 2015.
¹¹ Langer-Gould A, Brara SM, Beaber BE, Koebnick C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology. 2013;80:548–552.
¹² Gianfrancesco MA, Stridh P, Rhead B, et al. Evidence for a causal relationship between low Vitamin D, high BMI, and pediatric-onset MS. Neurology. 2017;88:1623-1629.
¹³ Barcellos LF, Shao X, Rhead B, et al. First genome-wide analysis in pediatric multiple sclerosis confirms a role for adult MS risk variants and reveals new candidates. Presentation. American Academy of Neurology (AAN) 68th Annual Meeting. Vancouver, British Columbia. April 15-21, 2016.
¹⁴ Gianfrancesco MA, Stridh P, Shao X, et al. Genetic risk factors for pediatric-onset multiple sclerosis, Mult Scler. 2017. doi: 10.1177/1352458517733551.