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European Journal of Pediatrics

, Volume 164, Issue 2, pp 61–69 | Cite as

Sudden and unexpected deaths after the administration of hexavalent vaccines (diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilius influenzae type b): is there a signal?

  • Rüdiger von Kries
  • André Michael Toschke
  • Klaus Straßburger
  • Michael Kundi
  • Helen Kalies
  • Uta Nennstiel
  • Gerhard Jorch
  • Joachim Rosenbauer
  • Guido Giani
Original Paper

Abstract

Deaths in temporal association with vaccination of hexavalent vaccines have been recently reported. The objective of this paper is to assess whether these temporal associations can be attributed to chance. Standardised mortality ratios (SMR) for deaths within 1 to 28 days after administration of either of the two hexavalent vaccines in the 1st and 2nd year of life were determined using the respective annual rates for sudden unexpected deaths (SUDs) from the national vital statistics. The distribution of SUD cases and the vaccination uptake by month were estimated from surveys and sales figures for the individual vaccines. Sensitivity analyses were performed to account for limitations in the data sources. For one of the vaccines, Vaccine B, all SMRs were well below one. For the other, Vaccine A, SMRs exceeded one insignificantly on the 1st day after vaccination in the 1st year of life. In the 2nd year of life, however, the SMRs for SUD cases within 1 day of vaccination with vaccine A were 31.3 (95% CI 3.8–113.1; two cases observed; 0.06 cases expected) and 23.5 (95% CI 4.8–68,6) for within 2 days after vaccination (three cases observed; 0.13 cases expected). Extensive sensitivity analyses could not attribute these findings to limitations of the data sources. Conclusion: These findings based on spontaneous reporting do not prove a causal relationship between vaccination and sudden unexpected deaths. However, they constitute a signal for one of the two hexavalent vaccines which should prompt intensified surveillance for unexpected deaths after vaccination.

Keywords

Safety Standardised mortality ratios Sudden unexpected death Vaccines 

Abbreviations

DTPa-IPV-HBV-Hib

diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilius influenzae type b

PEI

Paul Ehrlich Institute

SMR

standardised mortality ratio

SUD

sudden unexplained death

Notes

Acknowledgements

The reports for the SUD cases in temporal association with the administration of hexavalent vaccines were made available to us by Dr. Brigitte Keller-Stanislawski from the PEI, Langen, Germany. This work was supported by a grant from the PEI.

References

  1. 1.
    Bouvier-Colle MH, Flahaut A, Messiah A, Jougla E, Hatton F (1989) Sudden infant death and immunization: an extensive epidemiological approach to the problem in France—winter 1986. Int J Epidemiol 18: 121–126PubMedGoogle Scholar
  2. 2.
    Edwards IR, Biriell C (1994) Harmonisation in pharmacovigilance. Drug Safety 10: 93–102PubMedGoogle Scholar
  3. 3.
    Fine PE, Chen RT (1992) Confounding in studies of adverse reactions to vaccines. Am J Epidemiol 136: 121–135PubMedGoogle Scholar
  4. 4.
    Fleming PJ, Blair PS, Platt MW, Tripp J, Smith IJ, Golding J (2001) The UK accelerated immunisation programme and sudden unexpected death in infancy: case-control study. BMJ 322: 822PubMedGoogle Scholar
  5. 5.
    Gilbert RE, Fleming PJ, Azaz Y, Rudd PT (1990) Signs of illness preceding sudden unexpected death in infants. BMJ 300: 1237–1239PubMedGoogle Scholar
  6. 6.
    Golding J (1986) Immunisations. In: Butler NR, Golding J (eds) From birth to five: a study of the health and behaviour of Britains’ 5-year-olds. Pergamon Press, Oxford, pp 295–319Google Scholar
  7. 7.
    Griffin MR, Ray WA, Livengood JR, Schaffner W (1988) Risk of sudden infant death syndrome after immunization with the diphtheria-tetanus-pertussis vaccine. N Engl J Med 319: 618–623PubMedGoogle Scholar
  8. 8.
    Hoffman HJ, Hunter JC, Damus K, Pakter J, Peterson DR, van Belle G et al (1987) Diphtheria-tetanus-pertussis immunization and sudden infant death: results of the National Institute of Child Health and Human Development Cooperative Epidemiological Study of Sudden Infant Death Syndrome risk factors. Pediatrics 79: 598–611Google Scholar
  9. 9.
    Hutchins SS, Escolan J, Markowitz LE, Hawkins C, Kimbler A, Morgan RA et al (1989) Measles outbreak among unvaccinated preschool-aged children: opportunities missed by health care providers to administer measles vaccine. Pediatrics 83: 369–374Google Scholar
  10. 10.
    Jonville-Bera AP, Autret-Leca E, Barbeillon F, Paris-Llado J (2001) Sudden unexpected death in infants under 3 months of age and vaccination status—a case-control study. Br J Clin Pharmacol 51: 271–276Google Scholar
  11. 11.
    Keller-Stanislawski B, Löwer J (2003) Todesfälle in zeitlichem Zusammenhang mit Sechsfachimpfung. Kinder- und Jugendarzt 8: 608–613Google Scholar
  12. 12.
    Marks JS, Halpin TJ, Irvin JJ, Johnson DA, Keller JR (1979) Risk factors associated with failure to receive vaccinations. Pediatrics 64: 304–309Google Scholar
  13. 13.
    Mitchell EA, Stewart AW, Clements M (1995) Immunisation and the sudden infant death syndrome. New Zealand Cot Death Study Group. Arch Dis Child 73: 498–501PubMedGoogle Scholar
  14. 14.
    Platt MW, Blair PS, Fleming PJ, Smith IJ, Cole TJ, Leach CE et al (2000) A clinical comparison of SIDS and explained sudden infant deaths: how healthy and how normal? CESDI SUDI Research Group. Confidential Inquiry into Stillbirths and Deaths in Infancy study. Arch Dis Child 82: 98–106PubMedGoogle Scholar
  15. 15.
    Roberts SC (1987) Vaccination and cot deaths in perspective. Arch Dis Child 62: 754–759PubMedGoogle Scholar
  16. 16.
    Roper J, Day S (1988) Uptake of immunisations in low birth weight infants. Arch Dis Child 63: 518–521PubMedGoogle Scholar
  17. 17.
    Schmitt HJ, von Kries R, Hassenpflug B, Hermann M, Siedler A, Niessing W et al (2001) Haemophilus influenzae type b disease: impact and effectiveness of diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/ H. influenzae type b combination vaccines. Pediatr Infect Dis J 20: 767–774CrossRefPubMedGoogle Scholar
  18. 18.
    STIKO (2002) Empfehlungen der ständigen Impfkommission (STIKO)am Robert Koch-Institut/Stand Juli 2002. Epidemiol Bull 28: 227–242Google Scholar
  19. 19.
    Van Puijenbroek EP, van Grootheest K, Diemont WL, Leufkens HG, Egberts AC (2001) Determinants of signal selection in a spontaneous reporting system for adverse drug reactions. Br J Clin Pharmacol 52: 579–586Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Rüdiger von Kries
    • 1
  • André Michael Toschke
    • 1
  • Klaus Straßburger
    • 2
  • Michael Kundi
    • 3
  • Helen Kalies
    • 1
  • Uta Nennstiel
    • 4
  • Gerhard Jorch
    • 5
  • Joachim Rosenbauer
    • 2
  • Guido Giani
    • 2
  1. 1.Institut für Soziale Pädiatrie und Jugendmedizin der Ludwig-Maximilians-UniversitätMunichGermany
  2. 2.Abteilung Biometrie und EpidemiologieDeutsches Diabetes-ForschungsinstitutDüsseldorfGermany
  3. 3.Abteilung für Arbeits- und SozialhygieneInstitut für UmweltmedizinViennaAustria
  4. 4.Landesamt für Gesundheit und Lebensmittelsicherheit (Standort Oberschleissheim)OberschleissheimGermany
  5. 5.Zentrum für Kinderheilkunde der Otto-von-Guericke-UniversitätMagdeburgGermany

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