BACKGROUND: Although current rotavirus vaccines were not associated with an 
increased risk of intussusception in large trials before licensure, recent 
postlicensure data from international settings suggest the possibility of a 
small increase in risk of intussusception after monovalent rotavirus 
vaccination. We examined this risk in a population in the United States.
METHODS: Participants were infants between the ages of 4 and 34 weeks who were 
enrolled in six integrated health care organizations in the Vaccine Safety 
Datalink (VSD) project. We reviewed medical records and visits for 
intussusception within 7 days after monovalent rotavirus vaccination from April 
2008 through March 2013. Using sequential analyses, we then compared the risk of 
intussusception among children receiving monovalent rotavirus vaccine with 
historical background rates. We further compared the risk after monovalent 
rotavirus vaccination with the risk in a concurrent cohort of infants who 
received the pentavalent rotavirus vaccine.
RESULTS: During the study period, 207,955 doses of monovalent rotavirus vaccine 
(including 115,908 first doses and 92,047 second doses) were administered in the 
VSD population. We identified 6 cases of intussusception within 7 days after the 
administration of either dose of vaccine. For the two doses combined, the 
expected number of intussusception cases was 0.72, resulting in a significant 
relative risk of 8.4. For the pentavalent rotavirus vaccine, 1,301,810 doses 
were administered during the study period, with 8 observed intussusception cases 
(7.11 expected), for a nonsignificant relative risk of 1.1. The relative risk of 
chart-confirmed intussusception within 7 days after monovalent rotavirus 
vaccination, as compared with the risk after pentavalent rotavirus vaccination, 
was 9.4 (95% confidence interval, 1.4 to 103.8). The attributable risk of 
intussusception after the administration of two doses of monovalent rotavirus 
vaccine was estimated to be 5.3 per 100,000 infants vaccinated.
CONCLUSIONS: In this prospective postlicensure study of more than 200,000 doses 
of monovalent rotavirus vaccine, we observed a significant increase in the rate 
of intussusception after vaccination, a risk that must be weighed against the 
benefits of preventing rotavirus-associated illness. (Funded by the Centers for 
Disease Control and Prevention.).