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Ann Clin Transl Neurol. 2016 Nov 4;3(12):897-907. doi: 10.1002/acn3.365. eCollection 2016 Dec.

Distinct effects of obesity and puberty on risk and age at onset of pediatric MS.

Author information

Partners Pediatric Multiple Sclerosis Center Massachusetts General Hospital for Children Boston Massachusetts.
Department of Neurology University of California San Francisco California.
Pediatric Multiple Sclerosis Center Jacobs Neurological Institute SUNY Buffalo New York.
Lourie Center for Pediatric MS Stony Brook Children's Hospital Stonybrook New York.
Department of Pediatrics University of Utah Salt Lake City Utah.
Department of Pediatric Endocrinology Massachusetts General Hospital for Children Boston Massachusetts.
Pediatric MS Center at Loma Linda University Children's Hospital Loma Linda California.
Boston Children's Hospital Boston Massachusetts.
University of Utah/Primary Children's Hospital Salt Lake City Utah.
Department of Neurology UT Southwestern Dallas Texas.
Blue Bird Circle Multiple Sclerosis Center Baylor College of Medicine Houston Texas.
Pediatric Onset Demyelinating Diseases and Autoimmune Encephalitis Center St. Louis Children's Hospital Washington University School of Medicine St. Louis Missouri.
University of Alabama Center for Pediatric Onset Demyelinating Disease Children's Hospital of Alabama Birmingham Alabama.
Department of Neurology University of Utah Salt Lake City Utah.
Department of Pediatric Neurology Northwestern Feinberg School of Medicine Chicago Illinois.
Children's Hospital Colorado University of Colorado Denver Colorado.
Mayo Clinic's Pediatric MS Center Rochester Minnesota.
Department of Neurology University of Pennsylvania Philadelphia Pennsylvania.
Department of Neurology University of California San Francisco California; Department of Pediatrics Benioff Children's Hospital University of California San Francisco California.



The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS.


Case-control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex- and age-stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex-stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity.


Only 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001).


Higher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity.

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