Global epidemiology of vaccine-associated intussusception in children and adolescents, 1968 to 2024: An international pharmacovigilance study

Rotavirus vaccine associated intussusception has been investigated to some extent, limited research exists on intussusception caused by all vaccines from a comprehensive, global perspective. Thus, this study aimed to investigate the global burden of vaccine-associated intussusception using a comprehensive pharmacovigilance database. This study was conducted using data from the global pharmacovigilance database from 1968 to 2024. Reports of intussusception were identified by MedDRA code and categorized by vaccine type, age, sex, and region. Statistical disproportionality analysis was performed using reporting odds ratios (ROR) with 95% confidence interval (CI) and information components (IC) with IC025 to assess vaccine-specific signal detections. Among 35 million vaccine-associated total adverse events, 12,055 reports of vaccine-associated intussusception were identified. Rotavirus vaccines exhibited the strongest signal detections with intussusception (ROR, 70.16 [95% CI, 67.56-72.86]; IC, 5.27 [IC025, 5.22]), followed by diphtheria, tetanus, acellular pertussis, polio, and Haemophilus influenzae type b (ROR, 3.82 [95% CI, 3.67-3.97]; IC, 1.55 [IC025, 1.49]) and pneumococcal vaccines (ROR, 8.54 [95% CI, 8.13-8.96]; IC, 2.84 [IC025, 2.77]). The mean time to onset was 2.77 days, with a low fatality rate (0.07%). While our findings do not allow for causal conclusions, the results of this study suggest that rotavirus vaccines may be associated with a slight increase in the risk of intussusception. However, it is important to note that their benefits in preventing severe diarrheal disease far outweigh the risks.