Efficacy of Expressed Breast Milk Versus Sweet Solutions for Neonatal Procedural Pain: A Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy of expressed breast milk in reducing procedural pain in neonates compared with sweet solutions and to assess differences according to type of sweetener and timing of pain assessment. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials was conducted following PRISMA guidelines and registered in PROSPERO (CRD420261418093). PubMed/MEDLINE, Scopus, CINAHL, Cochrane Library, and Google Scholar were searched through May 2026. Random-effects models using standardized mean differences (Hedges' g) were applied. Heterogeneity was assessed using the I2 statistic. Meta-analyses were conducted by pain assessment time point, with subgroup and sensitivity analyses. Risk of bias was assessed using RoB 2 and certainty of evidence (CoE) using GRADE. Results: Seventeen randomized controlled trials were included. No statistically significant differences were observed between expressed breast milk and sweet solutions during the procedure (SMD = 0.15; 95% CI -0.18 to 0.47; I2 = 82.6%; Low CoE), at 1 min post-procedure (SMD = 0.40; 95% CI -0.11 to 0.92; I2 = 84.5%; Low CoE), or at 2 min post-procedure (SMD = 0.27; 95% CI -0.14 to 0.69; I2 = 7.9%; Moderate CoE). Subgroup analyses showed no significant differences or interactions. Egger's test detected significant funnel plot asymmetry during the procedure (intercept = -3.61; 95% CI -5.53 to -1.69; p = 0.005), but not at 1 min post-procedure (intercept = 1.84; 95% CI -3.53 to 7.20; p = 0.521). Conclusions: Current evidence suggests that expressed breast milk provides analgesia comparable to sweet solutions for neonatal procedural pain, although the certainty of the evidence is limited by substantial heterogeneity.