Pain response in newborns to the order of injecting BCG and hepatitis-B vaccines: A randomized trial

Objective: To determine if acute pain response after administration of the BCG vaccine and the Hepatitis-B vaccine is affected by the order in which they are given. Methods: This Single-center randomized clinical trial was conducted in the Vaccination room in the Pediatrics Outpatient Department at KVG Medical College; Karnataka, India. 76 healthy term neonates undergoing routine immunization were included in this study. Newborns received either BCG vaccine or the Hepatitis-B vaccine first, followed by the other vaccine. The primary outcome was neonatal pain during vaccine injection as assessed by a validated measure, the Neonatal Infant Pain Scale (NIPS), scored by resident doctors blinded to the study purpose and hypothesis. In addition, a nurse rated pain using a 10-cm visual analog scale(VAS). Results: A total of 76 infants participated: 38 received the BCG vaccine first and 38 received the Hepatitis-B vaccine first. Demographic characteristics did not differ between the groups. Overall mean (SD) pain scores per neonate were significantly lower when BCG was administered first compared to the order when Hepatitis-B vaccine was administered first (for NIPS 5.55 [0.54] vs. 5.84 [0.29], P=.005; for VAS, 6.25 [0.80] vs. 6.58 [0.54], P=.04). When given first, the BCG vaccine caused significantly less pain (P<.001)than the Hepatitis-B, as assessed by the NIPS and VAS (P<.001). Conclusions: Pain was reduced when the BCG vaccine was administered before the Hepatitis-B in neonates undergoing routine vaccination. The authors recommend that the order of vaccine injections be the BCG vaccine followed by Hepatitis-B.