title: Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus.
abstract: OBJECTIVE
  To evaluate suggested associations between childhood vaccinations, particularly against hepatitis B and Haemophilus influenzae type b, and risk of developing type 1 diabetes; and to determine whether timing of vaccination influences risk.
  
  
  METHODS
  We conducted a case-control study within 4 health maintenance organizations (HMOs) that participate in the Vaccine Safety Datalink project of the Centers for Disease Control and Prevention. Study eligibility was restricted to children who met the following criteria: 1) born during 1988 through 1997; 2) HMO member since birth; 3) continuously enrolled for first 6 months of life; and 4) at least 12 months of HMO membership before diabetes incidence date (or index date for controls) unless incidence date was before 12 months of age. All 4 HMOs maintain registries of their members who have diabetes, and we used the registries to identify potential cases of diabetes. We conducted chart reviews to verify that potential cases met the World Health Organization epidemiologic case definition for type 1 diabetes mellitus (ie, a physician's diagnosis of diabetes plus treatment with daily insulin injections). We defined the incidence date of diabetes as the first date that the child received a diagnosis of diabetes. We attempted to match 3 controls to each case. Controls had the same eligibility criteria as cases and were matched to individual cases on HMO, sex, date of birth (within 7 days), and length of health plan enrollment (up to the incidence or index date). The index date for controls was defined as the incidence date of the case to which the control was matched. Chart abstraction was performed by trained chart abstractors using standardized forms. In addition to complete vaccination histories, the chart abstraction forms for both cases and controls included information on sociodemographic characteristics, selected medical conditions, history of breastfeeding, and family medical history. We used conditional logistic regression to estimate the odds ratio (OR) of diabetes associated with vaccination, with vaccine exposure defined as before the diabetes incidence date (or index date for controls).
  
  
  RESULTS
  Two hundred fifty-two confirmed cases of diabetes and 768 matched controls met the study eligibility criteria. The OR (95% confidence interval) for the association with type 1 diabetes was 0.28 (0.07-1.06) for whole cell pertussis vaccine (predominantly in combination as diphtheria, tetanus toxoids and pertussis vaccine), 1.36 (0.70-2.63) for measles-mumps-rubella, 1.14 (0.51-2.57) for Haemophilus influenzae type b, 0.81 (0.52-1.27) for hepatitis B vaccine, 1.16 (0.72-1.89) for varicella vaccine, and 0.92 (0.53-1.57) for acellular pertussis-containing vaccines. Compared with children who had not received hepatitis B vaccine, the OR of diabetes was 0.51 (0.23-1.15) for children vaccinated at birth and 0.86 (0.54-1.35) for those first vaccinated against hepatitis B at 2 months of age or later. Race and ethnicity and family history of diabetes were independently associated with risk of type 1 diabetes, but adjustment for these factors did not materially alter the ORs for any of the vaccines.
  
  
  CONCLUSIONS
  In this large, population-based, case-control study, we did not find an increased risk of type 1 diabetes associated with any of the routinely recommended childhood vaccines. Our study adds to previous research by providing data on newer vaccines, including hepatitis B, acellular pertussis, and varicella vaccines. For the older vaccines, our results are generally in agreement with previous studies in not finding any increased risks. Ours is the first epidemiologic study to evaluate the possibility that timing of vaccination is related to risk of clinical diabetes in children. Our results on hepatitis B vaccine do not support the hypothesis; risk of type 1 diabetes was not different between infants vaccinated at birth and those who received their first vaccination later in life. The results of our study and the preponderance of epidemiologic evidence do not support an association between any of the recommended childhood vaccines and an increased risk of type 1 diabetes. Suggestions that diabetes risk in humans may be altered by changes in the timing of vaccinations also are unfounded.
authors.affiliation: National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA. fdestefano@cdc.gov
authors.forename: F
authors.initials: F
authors.lastname: DeStefano
authors.forename: J P
authors.initials: JP
authors.lastname: Mullooly
authors.forename: C A
authors.initials: CA
authors.lastname: Okoro
authors.forename: R T
authors.initials: RT
authors.lastname: Chen
authors.forename: S M
authors.initials: SM
authors.lastname: Marcy
authors.forename: J I
authors.initials: JI
authors.lastname: Ward
authors.forename: C M
authors.initials: CM
authors.lastname: Vadheim
authors.forename: S B
authors.initials: SB
authors.lastname: Black
authors.forename: H R
authors.initials: HR
authors.lastname: Shinefield
authors.forename: R L
authors.initials: RL
authors.lastname: Davis
authors.forename: K
authors.initials: K
authors.lastname: Bohlke
mesh_terms: D000293:Adolescent; D016667:Bacterial Capsules; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology*; D018073:Haemophilus Vaccines / Q000008:administration & dosage; D017325:Hepatitis B Vaccines / Q000008:administration & dosage; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D016015:Logistic Models; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage; D012306:Risk; D014611:Vaccination / Q000009:adverse effects / Q000706:statistics & numerical data*
chemical_list: D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D017325:Hepatitis B Vaccines; D011135:Polysaccharides, Bacterial