title: Factors that may explain observed associations between trivalent influenza vaccination and gastrointestinal illness in young children.
abstract: BACKGROUND
  Previously published studies reported an increased risk of gastrointestinal illness in the 14 days following trivalent influenza vaccination (TIV) in young children. While gastrointestinal illness may be a true adverse effect of TIV, other factors may influence this observed association, such as seasonal illness patterns and children being exposed to gastrointestinal pathogens at medical visits. The objective of this study was to examine factors influencing the association between TIV and gastrointestinal illness. Specifically, using data from a previous influenza vaccine safety study, we examined the association between medical encounters without TIV and gastrointestinal illness.
  
  
  METHODS
  Using electronic health record (EHR) data from 6 managed care organizations (MCOs), we identified medically attended gastrointestinal illness cases among children 24-59 months in the 2002-2006 influenza seasons. We matched each case to four controls on sex, birthdate (month/year), MCO, influenza season, and presence of a chronic condition. We then looked 1-14 days prior to the index date (gastrointestinal illness diagnosis date) to determine whether the child had a medical encounter. We excluded previous medical encounters with gastrointestinal-related diagnoses or TIV. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.
  
  
  RESULTS
  We identified 2062 gastrointestinal illness cases and matched them to 8248 controls. We observed increased odds of gastrointestinal illness within 14 days after a medical encounter (odds ratio=1.9; 95% confidence interval [CI]: 1.7-2.2) among children without chronic conditions. Among children with chronic conditions, the odds ratio was 3.9 (95% CI: 2.5-6.2).
  
  
  CONCLUSIONS
  We demonstrated that another exposure related to vaccination, medical visits, is also associated with increased odds for gastrointestinal illness. This study highlights challenges of interpreting results from observational vaccine safety studies when there are co-occurring exposures, and the importance of investigating confounding in EHR data, which are an essential resource for vaccine safety research.
authors.affiliation: Institute for Health Research, Kaiser Permanente Colorado, PO Box 378066, Denver, CO 80237, United States. sophia.r.newcomer@kp.org
authors.forename: Sophia R
authors.initials: SR
authors.lastname: Newcomer
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Hambidge
authors.forename: David L
authors.initials: DL
authors.lastname: McClure
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Daley
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.forename: Jason M
authors.initials: JM
authors.lastname: Glanz
mesh_terms: D000553:Ambulatory Care / Q000706:statistics & numerical data; D016022:Case-Control Studies; D002675:Child, Preschool; D002908:Chronic Disease; D016001:Confidence Intervals; D005260:Female; D005767:Gastrointestinal Diseases / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007252:Influenza Vaccines / Q000009:adverse effects*; D008297:Male; D016017:Odds Ratio; D012307:Risk Factors; D013997:Time Factors; D014611:Vaccination
chemical_list: D007252:Influenza Vaccines
keywords: CI; ED; Electronic medical records; GI; Gastrointestinal illness; ICD-9; Influenza vaccination; International Classification of Diseases – 9th revision; MCO; Observational research; SD; TIV; VSD; Vaccine Safety Datalink; confidence interval; emergency department; gastrointestinal; mOR; managed care organization; matched odds ratio; standard deviation; trivalent influenza vaccination