Risk of Intussusception After Rotavirus Vaccination

Abstract

Background: In 2013, the German Standing Committee on Vaccination (Ständige Impfkommission, STIKO) recommended rotavirus (RV) vaccination for all infants while stating that this mildly increased the risk of intussusception, a potentially life-threatening event. Since this recommendation was issued, multiple observational studies on this topic designed as self-controlled case series (SCCS) have been published. The SCCS design is particularly suitable for the study of rare adverse effects of medications.

Methods: We systematically searched the literature for SCCS studies on the risk of intussusception after RV vaccination. Relative risks (RR) corresponding to different doses of vaccine were summarized in a meta-analysis, and attributable risks (AR) were calculated.

Results: Of the 16 initially identified studies, 10 with a predominantly low risk of bias were considered in the analysis. The RR for intussusception was 5.71 (95% confidence interval [4.50; 7.25]) 1-7 days after the first dose, 1.69 [1.33; 2.14] after the second, and 1.14 [0.75; 1.74] after the third. The AR for children of the age at which RV vaccination is recommended was 1.7 [1.1; 2.7] additional intussusceptions per 100 000 vaccinated children after the first dose and 0.25 [0.16; 0.40] after the second. If >3-month-old infants are vaccinated, the AR is higher: 5.6 [4.3; 7.2] per 100 000 after the first dose and 0.81 [0.63; 1.06] per 100 000 after the second.

Conclusion: RV vaccination is associated with a markedly elevated RR and a mildly elevated AR for intussusception 1-7 days after the first dose. Physicians should begin the series of vaccinations at age 6-12 weeks, as recommended by the STIKO, because the risk of intussusception is higher afterward. Current health insurance company claim data indicate that 11.2% of infants are still receiving the first dose of the vaccine at ages above 3 months. The parents of vaccinated children should be informed about the possible signs of intussusception (colicky pain, bilious vomiting, and red "currant jelly" stool).

Figure 1

Risk of intussusception within 7 days following the first dose of vaccine 95% CI, 95% confidence interval; IV, inverse variance; SE, standard error

Figure 2

Risk of intussusception within 7 days following the second dose of vaccine 95% CI, 95% confidence interval; IV, inverse variance; SE, standard error

eFigure 1

Flow diagram showing literature search method DIMDI, German Institute of Medical Documentation and Information (Deutsches Institut für Medizinische Dokumentation und Information); RV, rotavirus

eFigure 2

Risk of intussusception within 7 days following the third dose of vaccine 95% CI, 95% confidence interval; IV, inverse variance; SE, standard error

eFigure 3

Risk of intussusception within 7 days following the first and second doses of vaccine—comparison of SCCS design and SCRI design studies 95% CI, 95% confidence interval; IV, inverse variance; RV, rotaviruses; RV1, monovalent vaccine; RV5, pentavalent vaccine; SCCS, self-controlled case series; SCRI, self-controlled risk interval; SE standard error

eFigure 4

Number of intussusceptions in infants aged <1 year; hospital discharge diagnoses taken from Federal Stastistical Office health reports, 2002–2014 RV, rotavirus; STIKO, German Standing Committee on Vaccination (Ständige Impfkommission)