Risk of intussusception following rotavirus vaccination: An evidence based meta-analysis of cohort and case-control studies.

BACKGROUND: International post-licensure studies on rotavirus vaccines have identified an increased risk of intussusception in infants after administration. The first developed rotavirus vaccine (Rotashield (RRV-TV)) was suspended post-licensure in 1999 after an association with intussusception was found. The currently available second-generation rotavirus vaccines (Rotateq (RV5) and Rotarix (RV1)), are recommended as a routine vaccine by the World Health Organisation (WHO). Post-licensure studies of these vaccines have shown a smaller but temporal increased risk for developing intussusception.

METHODS: A meta-analysis was performed to summarise available evidence and to give an overall risk of developing intussusception from case-control and cohort studies for all rotavirus vaccines that have been manufactured up to date. A search was conducted on MEDLINE, PubMed, EMBASE and Google Scholar up to May 2017. Eligible studies assessed the relationship between the rotavirus vaccine administration and subsequent development of intussusception both after receiving the first dose and after receiving all doses combined. Data was extracted on study characteristics, methods and outcomes. Results were pooled using the random-effect model.

RESULTS: Six cohort studies involving 4506265 total first doses and five case-control studies involving a total sample of 9643 children were included in this analysis. The cohort data revealed that there was an associated increased risk of intussusception after the first 7days post first dose of the vaccine (RR:3.71, 95% CI:1.08-12.69) and after receiving all doses of the rotavirus vaccine (RR:3.47, 95% CI:1.23-9.78). Similarly, the case-control data found an increased risk of intussusception following the first dose (OR: 8.45, 95% CI: 4.08-17.50) and following all doses (OR: 1.59, 95% CI: 1.11-2.27).

CONCLUSIONS: Findings of this meta-analysis suggest that the rotavirus vaccine is associated with an increased risk on the development of intussusception, principally seen after administration of the first dose of vaccine.