Breast Milk vs 24% Sucrose for Procedural Pain Relief in Preterm Neonates: A Non-inferiority Randomized Controlled Trial

Background: Oral sucrose is commonly used for pain relief in neonates during painful procedures. There is a paucity of data on the effect of breast milk (BM) in alleviating pain in preterm neonates.

Methods: This is a randomized, single-blinded, non-inferiority trial to test the hypothesis that BM is not inferior to 24% sucrose for procedural pain relief in neonates during blood draw by automated heel lance. IRB approval was obtained. Neonates born between 30 1/7 weeks and 36 6/7 weeks gestational age (GA) were included in the study within the first 30 days of birth. After obtaining parental consent, infants were randomly assigned to receive either 0.5 ml 24% sucrose or 2 ml expressed BM via syringe two minutes prior to scheduled heel lance. Two independent investigators assessed pain using Premature Infant Pain Profile-Revised (PIPP-R) scoring system at baseline, during the procedure, 30-, 60-, 90- and 120 seconds after completion of the procedure.
The primary outcome of this study was to compare PIPP-R scores during the procedure between the two groups. The secondary outcomes of the study included comparison of pain scores at 30-, 60-, 90- and120 seconds post-procedure. Statistical analysis included chi-square and t-test/ Wilcoxon rank-sum test as appropriate. Quantile regression analysis was conducted to estimate the effect of treatment at different quantiles (25th, 50th, and 75th percentile) of the PIPP-R score.

Results: Our cohort, (n=88) had a mean (SD) GA of 33 (1.6) weeks, birth weight of 1909 (530) grams; 50 (57%) were male, and 64 (73%) were African American. The baseline maternal and neonatal characteristics are shown in Table 1. PIPP-R scores during the procedure ranged from 5-12 in the two groups with a mean (SD) score of 8.3 (1.3). PIPP-R scores at 30 and 60 seconds post-procedure ranged from 0-6 and 0-5 with a mean (SD) of 4.14 (0.98) and 1.27 (1.88) at 30 and 60 seconds respectively. All infants reached their baseline by 90 seconds post-procedure (Figure 1).
The quantile regression estimates for PIPP-R scores during the procedure were statistically non-significant at all percentile levels of distribution. The set inferiority margin of 2 for the difference between groups was not crossed. The regression estimate at 75%ile level for PIPP-R scores at 60 seconds post-procedure were significantly higher in the sucrose group compared to the BM group (coefficient 1.98, SE 0.54 95% CI 0.92 to 3.05, p-value <0.001). Group-time interaction on linear mixed-effects regression was statistically significant at 60 seconds post-procedure suggesting a faster decline in the PIPP-R scores in the breast milk group compared to sucrose (p-value <0.001).

Conclusion: BM is not inferior to 24% sucrose in providing analgesia during heel lance in moderate and late preterm infants and it can be a safer alternative to sucrose.