Order of vaccine injection and infant pain response

Arch Pediatr Adolesc Med. 2009 May;163(5):469-72. doi: 10.1001/archpediatrics.2009.35.


Objective: To determine if acute pain response after administration of the diphtheria, polio, and tetanus toxoids and acellular pertussis and Haemophilus influenzae type b (DPTaP-Hib) vaccine and the pneumococcal conjugate vaccine (PCV) is affected by the order in which they are given.

Design: Single-center, double-blind, randomized clinical trial.

Setting: Outpatient pediatric clinic in Toronto, Ontario, Canada.

Participants: Healthy infants 2 to 6 months of age undergoing routine immunization.

Interventions: Infants received either their primary DPTaP-Hib vaccine or the PCV first, followed by the other vaccine.

Main outcome measures: The primary outcome was infant pain during vaccine injection as assessed by a validated measure, the Modified Behavioral Pain Scale (MBPS), using videotaped recordings of the procedure. In addition, parents rated pain using a 10-cm visual analog scale (VAS). Crying (yes/no) was also measured.

Results: The study was conducted between July 21, 2006, and June 21, 2007. A total of 120 infants participated: 60 received the DPTaP-Hib vaccine first and 60 received the PCV first. Infant characteristics did not differ between groups. Overall mean (SD) pain scores per infant after receiving both vaccine injections were significantly lower when DPTaP-Hib was administered first compared with when PCV was administered first (MBPS score, 7.6 [1.5] vs 8.2 [1.5], P = .037; parent VAS score, 4.2 [2.3] vs 5.6 [2.6], P = .003). When given first, the DPTaP-Hib vaccine caused significantly less pain (P < .001) than the PCV, as assessed by the MBPS, VAS, and crying.

Conclusions: Pain was reduced when the DPTaP-Hib vaccine was administered before the PCV in infants undergoing routine vaccination. We recommend that the order of vaccine injections be the DPTaP-Hib vaccine followed by the PCV.

Trial registration: ClinicalTrials.gov NCT00390130.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diphtheria-Tetanus-acellular Pertussis Vaccines / administration & dosage*
  • Double-Blind Method
  • Female
  • Haemophilus Vaccines / administration & dosage*
  • Haemophilus influenzae type b / immunology*
  • Humans
  • Infant
  • Injections
  • Male
  • Pain / etiology*
  • Pain Measurement
  • Pneumococcal Vaccines / administration & dosage*


  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Haemophilus Vaccines
  • Pneumococcal Vaccines

Associated data

  • ClinicalTrials.gov/NCT00390130