title: Intussusception risk after rotavirus vaccination in U.S. infants.
abstract: BACKGROUND
  International postlicensure studies have identified an increased risk of intussusception after vaccination with the second-generation rotavirus vaccines RotaTeq (RV5, a pentavalent vaccine) and Rotarix (RV1, a monovalent vaccine). We studied this association among infants in the United States.
  
  
  METHODS
  The study included data from infants 5.0 to 36.9 weeks of age who were enrolled in three U.S. health plans that participate in the Mini-Sentinel program sponsored by the Food and Drug Administration. Potential cases of intussusception and vaccine exposures from 2004 through mid-2011 were identified through procedural and diagnostic codes. Medical records were reviewed to confirm the occurrence of intussusception and the status with respect to rotavirus vaccination. The primary analysis used a self-controlled risk-interval design that included only vaccinated children. The secondary analysis used a cohort design that included exposed and unexposed person-time.
  
  
  RESULTS
  The analyses included 507,874 first doses and 1,277,556 total doses of RV5 and 53,638 first doses and 103,098 total doses of RV1. The statistical power for the analysis of RV1 was lower than that for the analysis of RV5. The number of excess cases of intussusception per 100,000 recipients of the first dose of RV5 was significantly elevated, both in the primary analysis (attributable risk, 1.1 [95% confidence interval, 0.3 to 2.7] for the 7-day risk window and 1.5 [95% CI, 0.2 to 3.2] for the 21-day risk window) and in the secondary analysis (attributable risk, 1.2 [95% CI, 0.2 to 3.2] for the 21-day risk window). No significant increase in risk was seen after dose 2 or 3. The results with respect to the primary analysis of RV1 were not significant, but the secondary analysis showed a significant risk after dose 2.
  
  
  CONCLUSIONS
  RV5 was associated with approximately 1.5 (95% CI, 0.2 to 3.2) excess cases of intussusception per 100,000 recipients of the first dose. The secondary analysis of RV1 suggested a potential risk, although the study of RV1 was underpowered. These risks must be considered in light of the demonstrated benefits of rotavirus vaccination. (Funded by the Food and Drug Administration.).
authors.affiliation: From the Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute (W.K.Y., T.A.L., M.K., R.P., G.M.L.), and the Division of Infectious Diseases and Department of Laboratory Medicine, Boston Children's Hospital (G.M.L.) - all in Boston; the Division of Research, Kaiser Permanente Northern California, Oakland (T.A.L.); the Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD (D.M., M.N.); Aetna, Blue Bell, PA (C.N.M.-W.); Government and Academic Research, HealthCore, Alexandria, VA (N.S.); and Comprehensive Health Insights, Humana, Louisville, KY (M.S.).
authors.forename: W Katherine
authors.initials: WK
authors.lastname: Yih
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Lieu
authors.forename: Martin
authors.initials: M
authors.lastname: Kulldorff
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Cheryl N
authors.initials: CN
authors.lastname: McMahill-Walraven
authors.forename: Richard
authors.initials: R
authors.lastname: Platt
authors.forename: Nandini
authors.initials: N
authors.lastname: Selvam
authors.forename: Mano
authors.initials: M
authors.lastname: Selvan
authors.forename: Grace M
authors.initials: GM
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Nguyen
mesh_terms: D015331:Cohort Studies; D006801:Humans; D007117:Immunization, Secondary; D007223:Infant; D007443:Intussusception / Q000453:epidemiology / Q000209:etiology*; D012306:Risk; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D014481:United States / Q000453:epidemiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C492457:RIX4414 vaccine; C492535:RotaTeq; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated