title: A method for reporting and classifying acute infectious diseases in a prospective study of young children: TEDDY.
abstract: BACKGROUND
  Early childhood environmental exposures, possibly infections, may be responsible for triggering islet autoimmunity and progression to type 1 diabetes (T1D). The Environmental Determinants of Diabetes in the Young (TEDDY) follows children with increased HLA-related genetic risk for future T1D. TEDDY asks parents to prospectively record the child's infections using a diary book. The present paper shows how these large amounts of partially structured data were reduced into quantitative data-sets and further categorized into system-specific infectious disease episodes. The numbers and frequencies of acute infections and infectious episodes are shown.
  
  
  METHODS
  Study subjects (n = 3463) included children who had attended study visits every three months from age 3 months to 4 years, without missing two or more consecutive visits during the follow-up. Parents recorded illnesses prospectively in a TEDDY Book at home. The data were entered into the study database during study visits using ICD-10 codes by a research nurse. TEDDY investigators grouped ICD-10 codes and fever reports into infectious disease entities and further arranged them into four main categories of infectious episodes: respiratory, gastrointestinal, other, and unknown febrile episodes. Incidence rate of infections was modeled as function of gender, HLA-DQ genetic risk group and study center using the Poisson regression.
  
  
  RESULTS
  A total of 113,884 ICD-10 code reports for infectious diseases recorded in the database were reduced to 71,578 infectious episodes, including 74.0% respiratory, 13.1% gastrointestinal, 5.7% other infectious episodes and 7.2% febrile episodes. Respiratory and gastrointestinal infectious episodes were more frequent during winter. Infectious episode rates peaked at 6 months and began declining after 18 months of age. The overall infectious episode rate was 5.2 episodes per person-year and varied significantly by country of residence, sex and HLA genotype.
  
  
  CONCLUSIONS
  The data reduction and categorization process developed by TEDDY enables analysis of single infectious agents as well as larger arrays of infectious agents or clinical disease entities. The preliminary descriptive analyses of the incidence of infections among TEDDY participants younger than 4 years fits well with general knowledge of infectious disease epidemiology. This protocol can be used as a template in forthcoming time-dependent TEDDY analyses and in other epidemiological studies.
authors.affiliation: University of Tampere, Tampere, Finland. maria.lonnrot@uta.fi.|Seinäjoki Central Hospital, Seinäjoki, Finland. maria.lonnrot@uta.fi.
authors.forename: Maria
authors.initials: M
authors.lastname: Lönnrot
authors.affiliation: University of South Florida, Tampa, USA. kristian.lynch@epi.usf.edu.
authors.forename: Kristian
authors.initials: K
authors.lastname: Lynch
authors.affiliation: Lund University, Malmö, Sweden. helena.larsson@med.lu.se.
authors.forename: Helena Elding
authors.initials: HE
authors.lastname: Larsson
authors.affiliation: Lund University, Malmö, Sweden. ake.lernmark@med.lu.se.
authors.forename: Åke
authors.initials: Å
authors.lastname: Lernmark
authors.affiliation: Barbara Davis Center for Childhood Diabetes, Denver, CO, USA. marian.rewers@ucdenver.edu.
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.affiliation: Pacific Northwest Diabetes Research Institute, Seattle, USA. wah@u.washington.edu.
authors.forename: William
authors.initials: W
authors.lastname: Hagopian
authors.affiliation: Georgia Regents University, Augusta, USA. jshe@gru.edu.
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.affiliation: University of Turku, Turku, Finland. olli.simell@utu.fi.
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V, Neuherberg, Germany. anette-g.ziegler@helmholtz-muenchen.de.
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
authors.affiliation: NIH, Bethesda, USA. akolkarb@extra.niddk.nih.gov.
authors.forename: Beena
authors.initials: B
authors.lastname: Akolkar
authors.affiliation: University of South Florida, Tampa, USA. jeffrey.krischer@epi.usf.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Krischer
authors.affiliation: University of Tampere, Tampere, Finland. heikki.hyoty@uta.fi.|Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland. heikki.hyoty@uta.fi.
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
mesh_terms: D015551:Autoimmunity; D002675:Child, Preschool; D003141:Communicable Diseases / Q000145:classification* / Q000453:epidemiology*; D066264:Datasets as Topic; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000209:etiology; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D038801:International Classification of Diseases; D008297:Male; D010290:Parents; D011446:Prospective Studies; D012307:Risk Factors; D057566:Self Report