August 2, 2011 — The trivalent inactivated influenza vaccine (TIV) does not seem to be associated with serious adverse events, say the authors of a self-controlled screening study of more than 60,000 children.
Lead author Jason M. Glanz, PhD, from the Institute for Health Research, Kaiser Permanente, Denver, Colorado, and colleagues screened children 24 to 59 months of age who were enrolled in 7 managed care organizations over 4 influenza seasons between October 1, 2002, and March 31, 2006. "To our knowledge, this investigation represents the largest TIV screening study for children [in this age range] to date," they write in the August issue of the Archives of Pediatric & Adolescent Medicine.
They observed a significant, temporal relationship between vaccine administration and only 4 acute, nonserious conditions: fever and limb soreness, which were known adverse events, and vomiting and diarrhea, which had been identified in earlier safety studies.
Annual influenza vaccination was first recommended for children aged 6 to 23 months in 2004, write Dr. Glanz and his coauthors. The age range was gradually expanded to 18 years by 2008. However, although vaccine efficacy can be demonstrated through direct observation, its safety must be inferred from a relative lack of adverse events associated temporally with administration. This makes large, postmarketing studies important vehicles for detecting adverse events, particularly rare and serious ones that may have been missed in prelicensure clinical trials. One study examined safety in all children under 18 years of age, but it was conducted before the expanded age recommendations. Dr. Glanz and colleagues' study is the first to gather safety data specifically for the 24-month to 59-month age group.
The authors looked for evidence of medically attended events (MAEs) in children aged 24 to 59 months who had received at least 1 TIV dose during the study period. Multiple vaccinations in the same child were treated as independent exposures. The investigators used a self-controlled case series analysis to examine the temporal relationship between TIV and the incidence of MAEs. In this type of analysis, "the incidence rate of events in postvaccination risk windows is compared with the incidence rate in unexposed periods before and after the risk windows. Only individuals who experience the event of interest are included in the analysis, and each individual acts as his or her own control." This design controls for potentially confounding variables such as sex, race or ethnicity, and chronic health conditions, the authors explain. Overall, the study cohort included 66,283 children who received 91,692 doses of TIV.
The investigators studied the records for 5 potentially serious MAEs: cellulitis and skin reactions, hypotension, cardiac events, nervous system disorders, and gastrointestinal (GI) tract disorders. When the data were restricted to events confirmed through medical records, the only condition significantly associated with vaccination was aggregated GI tract disorders in children with a high-risk health condition (incidence rate ratio [IRR], 7.7; 95% confidence interval [CI], 1.11 - 53.52; P = .04). Other conditions significantly associated with TIV were GI tract symptoms, such as vomiting and diarrhea (IRR, 1.18; 95% CI, 1.1 - 1.25), and fever (IRR, 1.71; 95% CI, 1.64 - 1.80). There was also an association with nonconfirmed reports of limb soreness (IRR, 3.56; 95% CI, 1.3 - 9.75; P = .01).
In a secondary analysis examining the risk for MAEs in children who received multiple doses of TIV, the authors observed an apparent dose response between the vaccine and allergic reactions in the 1- to 3-day risk window. "The respective IRRs for the second through the fifth doses increased incrementally from 6.19 to 16.45 and were statistically significant," they write.
Numerous associations were examined in an effort to maximize the detection of important safety signals, so it is possible that statistically significant signals may have appeared simply by chance, the authors state. Also, they obtained their data from managed care organizations, which did not keep these statistics for research purposes, so some of the MAEs may have been misclassified. In addition, some rare adverse events may have been missed, despite the large cohort size.
Nevertheless, they conclude, "our results provide additional evidence that TIV is safe in young children."
This study was funded through a subcontract with America’s Health Insurance Plans under a contract from the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.
Arch Pediatr Adolesc Med. 2011;165:749-755. Abstract
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Cite this: Study Confirms Safety of Pediatric Flu Vaccine - Medscape - Aug 02, 2011.