The analgesic effects of human milk odor in preterm neonates: a systematic review and meta-analysis.

Abstract

Preterm neonates frequently undergo a variety of painful and invasive procedures. Neonatal pain has been associated with changes in hormone levels, tissue damage, and brain development. Nonpharmacological approaches, such as the use of breast milk odor, have been investigated as a strategy to reduce those effects. However, its efficacy remains unclear, and further research is needed to establish its true therapeutic value.

Purpose: Evaluate the analgesic effects of breast milk odor in premature neonates.

Methods: We systematically searched PubMed, EMBASE, and Cochrane for randomized controlled trials (RCTs) assessing the effects of human milk odor compared with no aromatherapy (control) or placebo (odorless diffuser/distilled water/saline) on pain relief, oxygen saturation (SaO₂), and heart rate in preterm neonates undergoing invasive procedures. Two independent reviewers screened studies and extracted data up to July 5, 2025. Statistical analyses were conducted using RevMan Web (version 8.0.0) for the primary meta-analyses, and R software was used to perform sensitivity analyses.

Results: Among 460 references identified, eight randomized controlled trials met the inclusion criteria, totaling 451 preterm neonates, of whom 225 (49.9%) were exposed to human milk odor. The mean gestational age was 33.56 ± 2.58 weeks, and 226 (50.1%) were male. Two studies were conducted using venipuncture as a painful procedure, four used the heel prick test, one used peripheral catheterization, and one used vaccination. Compared with the control group and the placebo, the group exposed to the milk odor showed a reduction in pain scores during the painful procedure (SMD = -0.95; 95% CI: -1.45 to -0.45; p = 0.0002; I² = 84%). The subgroup analysis of the five RCTs that used the PIPP score for the pain assessment showed similar results; the human milk odor-exposed group showed a lower pain score compared with the control group (MD -2.66; 95% CI -4.25 to -1.06; p = 0.001). Secondary outcomes included physiological parameters such as heart rate and oxygen saturation (SaO₂). Neonates exposed to breast milk odor exhibited lower heart rates compared to control (MD = -9.26; 95% CI: -14.28 to -4.24; p = 0.0003; I² = 27%). Oxygen saturation was also higher in the intervention group (MD = 2.40; 95% CI: 0.68-4.12; p = 0.006; I² = 53%) CONCLUSION: Aromatherapy with human breast milk reduces pain in neonates. Larger studies are needed to validate our results.