Vaccination and unexplained sudden death risk in Taiwanese infants

Pharmacoepidemiol Drug Saf. 2017 Jan;26(1):17-25. doi: 10.1002/pds.4141. Epub 2016 Nov 28.


Purpose: In March 1992, eight infants who had died within 36 hours of receiving whole-cell pertussis vaccine (diphtheria, tetanus, and whole-cell pertussis [DTwP]) prompted the Taiwan health authorities to suspend its use. We conducted an investigation of vaccination and sudden unexplained infant death (SUID) and repeated it more recently after Taiwan switched to acellular pertussis vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]) in 2010.

Methods: All SUIDs aged 31-364 days during 1990-1992 and 1996-2013 were selected from the death registration databases. The case-control investigation matched each case to two controls on clinic, sex, and birth date, whereas the follow-up self-controlled case series study compared risk of death during the 30-day post-vaccination risk periods with those in the control periods within the same case.

Results: Sudden unexplained infant death was associated with never receiving DTwP (odds ratio 2.28, 95% confidence interval 1.25-4.15) in the case-control investigation. The odds ratios within 0-1, 2-7, 8-14, and 15-30 days of DTwP administration were 1.18, 0.26, 0.50, and 0.77. In the 1996-2013 self-controlled case series studies, this temporal shift between DTwP and SUID was consistently observed for female (incidence rate ratio 1.70, 0.75, 1.01, and 0.84) but not male or DTaP recipients. A pooled analysis showed significant risk within 2 days of receiving DTwP in female infants (incidence rate ratio 1.66, 95% confidence interval 1.05-2.60).

Conclusions: Being unvaccinated and recent receipt of DTwP in female infants was significantly associated with SUID; the latter was consistent with a temporal shift pattern without overall increase in risk. The currently used pertussis vaccine, DTaP, did not increase risk of SUID. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: DTP; OPV; case-control studies; pharmacoepidemiology; self-controlled case series; sex-differential effect; sudden death.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Case-Control Studies
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage*
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / administration & dosage*
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Risk
  • Sudden Infant Death / epidemiology*
  • Sudden Infant Death / etiology
  • Taiwan / epidemiology
  • Time Factors
  • Vaccination / adverse effects
  • Vaccination / methods


  • Diphtheria-Tetanus-Pertussis Vaccine
  • Diphtheria-Tetanus-acellular Pertussis Vaccines