Background: There are preliminary data to suggest that pain experienced in the neonatal period may have long-lasting effects on the infant. The objectives of this study were to determine whether circumcised infants differ in their pain response at 4 or 6 month vaccination compared to uncircumcised infants, and if vaccination response is affected by pre-treatment of circumcision pain with the topical anesthetic cream EMLA.

Methods: Prospective cohort study which included uncircumcised infants (group 1), and infants who had been randomized to received EMLA (group 2) or placebo (group 3) prior to neonatal circumcision. Parents consented to have their infants videotaped during vaccination at the infant's primary care physician's clinic. Videotapes were scored by a blinded research assistant for facial activity, cry duration and visual analogue scale (VAS) pain scores.

Results: 87 infants participated in the study. Birth characteristics and infant characteristics at the time of vaccination, including age and temperament scores, did not differ significantly among groups. MANOVA revealed a significant multivariate group effect (p<0.001) using difference (vaccination - baseline) values for% facial activity,% cry, and VAS pain scores. Univariate ANOVAs were significant for all outcome measures: group 3 had higher difference scores than group 1 for% facial action(136.9% vs. 77.5%),% cry duration (53.8% vs. 24.7%), and VAS pain scores (5.1 cm vs. 3.1 cm), p<0.05. In addition, VAS pain scores in group 3 were significantly higher than group 2 (3.3 cm), p<0.05. There was a significant linear trend on all outcomes, showing increasing pain scores from groups 1 to 3.

Conclusion: Circumcised infants demonstrated an increased pain response to routine vaccination. Pretreatment of neonatal circumcision pain with EMLA attenuated vaccination response. It is postulated that infant `pain memories' account for the observed results. Treatment of neonatal circumcision pain is recommended.