title: Distinct effects of obesity and puberty on risk and age at onset of pediatric MS.
abstract: 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.
authors.affiliation: Partners Pediatric Multiple Sclerosis Center Massachusetts General Hospital for Children Boston Massachusetts.
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.affiliation: Department of Neurology University of California San Francisco California.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Graves
authors.affiliation: Pediatric Multiple Sclerosis Center Jacobs Neurological Institute SUNY Buffalo New York.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: Lourie Center for Pediatric MS Stony Brook Children's Hospital Stonybrook New York.
authors.forename: Anita
authors.initials: A
authors.lastname: Belman
authors.affiliation: Department of Pediatrics University of Utah Salt Lake City Utah.
authors.forename: Cody
authors.initials: C
authors.lastname: Olsen
authors.affiliation: Department of Pediatric Endocrinology Massachusetts General Hospital for Children Boston Massachusetts.
authors.forename: Madhusmita
authors.initials: M
authors.lastname: Misra
authors.affiliation: Pediatric MS Center at Loma Linda University Children's Hospital Loma Linda California.
authors.forename: Gregory
authors.initials: G
authors.lastname: Aaen
authors.affiliation: Boston Children's Hospital Boston Massachusetts.
authors.forename: Leslie
authors.initials: L
authors.lastname: Benson
authors.affiliation: University of Utah/Primary Children's Hospital Salt Lake City Utah.
authors.forename: Meghan
authors.initials: M
authors.lastname: Candee
authors.affiliation: Boston Children's Hospital Boston Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Gorman
authors.affiliation: Department of Neurology UT Southwestern Dallas Texas.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Greenberg
authors.affiliation: Lourie Center for Pediatric MS Stony Brook Children's Hospital Stonybrook New York.
authors.forename: Lauren
authors.initials: L
authors.lastname: Krupp
authors.affiliation: Blue Bird Circle Multiple Sclerosis Center Baylor College of Medicine Houston Texas.
authors.forename: Timothy
authors.initials: T
authors.lastname: Lotze
authors.affiliation: Pediatric Onset Demyelinating Diseases and Autoimmune Encephalitis Center St. Louis Children's Hospital Washington University School of Medicine St. Louis Missouri.
authors.forename: Soe
authors.initials: S
authors.lastname: Mar
authors.affiliation: University of Alabama Center for Pediatric Onset Demyelinating Disease Children's Hospital of Alabama Birmingham Alabama.
authors.forename: Jayne
authors.initials: J
authors.lastname: Ness
authors.affiliation: Department of Neurology University of Utah Salt Lake City Utah.
authors.forename: John
authors.initials: J
authors.lastname: Rose
authors.affiliation: Department of Pediatric Neurology Northwestern Feinberg School of Medicine Chicago Illinois.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rubin
authors.affiliation: Children's Hospital Colorado University of Colorado Denver Colorado.
authors.forename: Teri
authors.initials: T
authors.lastname: Schreiner
authors.affiliation: Mayo Clinic's Pediatric MS Center Rochester Minnesota.
authors.forename: Jan
authors.initials: J
authors.lastname: Tillema
authors.affiliation: Department of Neurology University of Pennsylvania Philadelphia Pennsylvania.
authors.forename: Amy
authors.initials: A
authors.lastname: Waldman
authors.affiliation: Mayo Clinic's Pediatric MS Center Rochester Minnesota.
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: Department of Pediatrics University of Utah Salt Lake City Utah.
authors.forename: Charlie
authors.initials: C
authors.lastname: Casper
authors.affiliation: Department of Neurology University of California San Francisco California; Department of Pediatrics Benioff Children's Hospital University of California San Francisco California.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant