The effect of breast milk odor on infant pain and stress levels: a systematic review and meta-analysis

BACKGROUND: Effective management of neonatal pain and stress is crucial, with non-pharmacological approaches like maternal odor showing promise. However, mixed evidence exists on its efficacy. This study aims to comprehensively assess the effects of breast milk odor on pain and stress (primary outcomes) and on oxygen saturation (SpO2) and heart rate (secondary outcomes) in neonates. METHODS: A thorough search was conducted on PubMed, Cochrane, SID, Embase, and Google Scholar until January 14, 2025, without time restrictions. A meta-analysis was performed to compare outcomes between intervention and control groups, assessing heterogeneity using the I2 statistic and chi-squared test. A random effects model was applied for high heterogeneity (I2 >= 30%, p < 0.05), analyzing continuous outcomes with mean difference (MD) and standardized mean difference (SMD) at a 95% confidence interval (CI). Subgroup analyses were conducted based on newborn procedures and term status, along with meta-regression and sensitivity analyses. Trial Sequential Analysis (TSA) was employed to ensure reliable conclusions about the intervention effects, and the certainty of evidence was evaluated using GRADE. RESULTS: The systematic review included seven studies (RCT and quasi-experimental) revealing that breast milk odor significantly reduces pain responses in neonates (SMD: -1.60, 95% CI: -2.48, -0.72; I² = 94%; 7 trials; 478 neonates; low-certainty evidence). It also improved key physiological parameters, such as oxygen saturation (MD: 1.64, 95% CI: 0.49, 2.80; I² = 57%; 5 trials; 288 neonates; very low-certainty evidence) and heart rate (MD: -6.73, 95% CI: -12.33, -1.13; I2 = 78%; 5 trials; 288 neonates; very low-certainty evidence). Although a reduction in stress levels was noted, it did not reach statistical significance (MD: -0.64, 95% CI: -1.87, 0.59; I2 = 89%; 2 trials; 128 neonates; very low-certainty evidence). Meta-regression indicated a significant correlation between cesarean delivery rates and neonatal pain response (p = 0.010). TSA results confirmed the analysis was adequately powered for pain outcome. CONCLUSION: The review underscores the potential of breast milk odor as a non-pharmacological intervention for managing pain in neonates. However, the low to very low certainty of evidence calls for further research to validate these findings and improve neonatal care protocols.