After an evaluation of 800,000 doses of pentavalent rotavirus vaccinations in U.S. infants, researchers reported in the February 8 issue of JAMA that there is no increased risk of intussusception after vaccination, despite some previous data indicating that those infants who received the vaccine were at potential increased risk. Intussusception is a condition whereby a portion of the small or large intestine slides forward into itself, like a telescope.

The researchers' background information says that:

"In 1999, the rhesus tetravalent rotavirus vaccine (RRV, Rotashield) was withdrawn from the U.S. market due to a significantly increased risk of intussusception following vaccination. Since then, 2 vaccines to prevent rotavirus infection have been licensed for use in the United States: a pentavalent rotavirus vaccine (RV5, RotaTeq) in 2006 and a monovalent rotavirus vaccine (RV1, Rotarix) in 2008."

Scientists performed large prelicensure trials due to the previous link between RRV and intussusception but observed no increased risk, "however, 2 recent international postlicensure evaluations [conducted in Australia, Mexico and Brazil] have observed an increased risk of intussusception in the first week after administration of the first dose of rotavirus vaccines."

Irene M. Shui, Sc.D., of Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston and her team decided to re-evaluate the risk of intussusception in relation to the rotavirus vaccination, whilst focusing specifically on the 1- to 7-day risk window after the first dose was administered. The study involved infants between the ages from 4 to 34 weeks who were enrolled in the Vaccine Safety Datalink (VSD) receiving RV5 from May 2006 to February 2010.

Amongst others, the researchers analyzed the comparison of intussusception rates in infants who had received RV5 with intussusception rates in infants who received other recommended vaccines without RV5 during the same period. They included data on the expected number of intussusception visits based on background rates that were examined before RV5 was licensed in the U.S. (2001-2005).

From 786,725 doses of RV5 administered from May 2006 to February 2010, 39% or 309,844 vaccinations consisted of first doses, 33% of second and 28% were third doses from a comparison cohort of 389,026 visits.

After adjusting for age, both analyse,s the combined dose or dose-specific analysis, showed no statistically important higher risks of intussusception in both windows, the 1- to 30-day and the 1- to 7-day risk window.

The researchers observed 21 incidents of intussusception in the 1- to 30-day window after all RV5 doses were administered compared with 20.9 expected cases, whilst they noted 7 cases compared with 5.7 expected incidents after administration of the first dose. In the 1- to 7-day window after all RV5 doses were given, they observed 4 incidents instead of 4.3 expected cases whilst after the first dose they noted 1 incident compared with a 0.8 expected incident.

The researchers declare:

"Based on our analysis, an excess risk of 1 intussusception event per 65,287 RV5 vaccines following dose 1 can be reliably excluded, although we cannot rule out the possibility of a lower-level risk."

They state that the reasons for the inconsistent results between different studies remain unclear and continue saying:

"Because intussusception is a rare event, we cannot rule out a chance finding of risk in Australia and Mexico as well as the possibility of not detecting a low-level risk in the United States and Brazil. Another possible explanation might be effect modification of the rotavirus vaccine-intussusception association by an environmental or genetic factor that differs between the populations."

They researchers conclude:

"In this large, prospective postlicensure safety monitoring study of almost 800,000 doses of RV5 vaccine, with more than 300,000 first doses, we did not observe any increased risk of intussusception following RV5 vaccination.

The introduction of rotavirus vaccines has had a substantial public health effect on severe rotavirus disease in U.S. infants. Although we cannot entirely exclude the possibility of a very low-level risk, the findings of our study strengthen the evidence base in favor of vaccination for effective control of severe childhood rotavirus disease."

Written by Petra Rattue