title: Perinatal and early childhood risk factors associated with rheumatoid factor positivity in a healthy paediatric population.
abstract: OBJECTIVE
  To examine perinatal and childhood risk factors for the presence of rheumatoid factor in healthy children.
  
  
  METHODS
  The Diabetes Autoimmunity Study in the Young (DAISY) is a longitudinal study of children at increased risk of type 1 diabetes, based on possession of human leucocyte antigen (HLA)-DR4 and DR3 alleles or a family history of diabetes. 651 children who participated in DAISY, with an average age of 6.4 (range 1-15) years, were tested for the presence of rheumatoid factor in their most recent serum sample. 23 children were positive for rheumatoid factor. Exposure data were collected prospectively by interview. HLA-DR4 alleles were identified using polymerase chain reaction-based Class II genotyping.
  
  
  RESULTS
  While exploring risk factors for rheumatoid factor positivity in a multivariate model, several important interaction terms involving HLA-DR4 status suggested the need to evaluate risk factors in HLA-DR4-positive and HLA-DR4-negative children separately. In HLA-DR4-negative children, rheumatoid factor-positive infants were less likely to have been breast fed for >3 months (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04 to 0.99), more likely to have been exposed to non-parental tobacco smoke (OR 5.38; 95% CI 0.93 to 31.27) and more likely to be a race/ethnicity other than non-Hispanic white (OR 6.94; 95% CI 1.10 to 43.88) compared with rheumatoid factor-negative children, after adjusting for age, sex and maternal education. In HLA-DR4-positive children, there were no significantly associated risk factors for rheumatoid factor positivity.
  
  
  CONCLUSIONS
  Risk factors for rheumatoid factor positivity in children vary by HLA-DR4 genotype. In HLA-DR4-negative children, breast feeding may decrease the risk, and environmental tobacco smoke may increase the risk, of autoimmunity.
authors.affiliation: Department of Preventive Medicine and Biometrics, University of Colorado at Denver and Health Sciences Center, 4200 East Ninth Avenue, Box B119, Denver, CO 80262, USA.
authors.forename: Kendra A
authors.initials: KA
authors.lastname: Young
authors.forename: Lezlie A
authors.initials: LA
authors.lastname: Parrish
authors.forename: Gary O
authors.initials: GO
authors.lastname: Zerbe
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Deane
authors.forename: V
authors.initials: V
authors.lastname: Michael Holers
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
mesh_terms: D000367:Age Factors; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics; D001903:Bottle Feeding; D002648:Child; D002675:Child, Preschool; D005006:Ethnicity; D005260:Female; D005838:Genotype; D015804:HLA-DR4 Antigen / Q000097:blood*; D006650:Histocompatibility Testing; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000032:analysis*; D012307:Risk Factors; D012737:Sex Factors; D014028:Tobacco Smoke Pollution
chemical_list: D015804:HLA-DR4 Antigen; D014028:Tobacco Smoke Pollution; D012217:Rheumatoid Factor