In the delicate world of neonatal care, managing pain in preterm infants represents a critical and complex challenge. These vulnerable newborns routinely endure numerous painful and invasive procedures during their early days of life, which can have profound consequences on their developing physiology and neurobiology. Recent scientific inquiry has turned its attention to nonpharmacological pain relief methods, which could offer gentle yet effective analgesia without the risks associated with drug therapies. Among these emerging modalities, the scent of human breast milk has attracted considerable interest for its potential to alleviate pain responses in preterm neonates. Despite this intriguing premise, rigorous evaluations of breast milk odor as an analgesic intervention have yet to yield unequivocal conclusions. A comprehensive systematic review and meta-analysis recently published in the Journal of Perinatology by Bertol et al. delves deeply into this subject, aiming to clarify the therapeutic value of human milk odor in neonatal pain management.
The administration of pain relief in preterm infants holds significant clinical relevance beyond immediate comfort. Research spanning molecular to behavioral domains has firmly established that untreated or inadequately treated pain in neonates can alter physiological parameters, including stress hormone fluctuations, and adversely affect brain development trajectories with long-term cognitive and emotional ramifications. These consequences have galvanized neonatal care providers and researchers to explore interventions that are both effective and minimally disruptive. Pharmacological analgesics, while valuable, often bear concerns regarding safety, dosing complexity, and potential neurologic side effects, prompting investigations into adjunct or alternative nonpharmacological strategies that harness natural sensory stimuli.
Olfactory stimulation, particularly involving maternal-related odors, has surfaced as a promising non-invasive approach owing to the infant’s early developed sense of smell and innate familiarity with maternal scents. Breast milk, as a uniquely maternal biological fluid, emits a complex olfactory profile composed of volatile organic compounds that may convey comforting cues to the neonate. This biochemical signature is theorized to modulate neonatal autonomic and central nervous system responses, potentially attenuating the perception or physiological correlates of pain. Experimental studies have examined whether exposure to breast milk odor during painful procedures, such as heel lances or venipunctures, can dampen pain responses measured by behavioral pain scales, heart rate variability, and hormonal markers such as cortisol.
Bertol and colleagues undertook a rigorous meta-analytical approach to synthesize the extant evidence from randomized controlled trials and observational studies examining analgesic outcomes associated with breast milk odor exposure in preterm neonates. Their meta-analysis pooled data from multiple investigations differing in methodology, setting, and sample size, providing a higher statistical power to detect subtle analgesic effects than individual studies alone. The researchers meticulously assessed pain scores, physiological parameters, and biochemical stress markers to offer a multidimensional evaluation of the intervention’s efficacy.
The findings from this meta-analysis paint a nuanced picture. While some studies reported statistically significant reductions in pain indicators and stress hormones when neonates were exposed to breast milk odor during painful procedures, other trials showed minimal or no clear benefit compared to control conditions such as no intervention or alternative odors. This heterogeneity of results underscores the complexity of neonatal pain modulation and suggests that multiple factors, including methodological variations and infant-specific variables, may influence the effectiveness of maternal milk odor as an analgesic stimulus.
Mechanistic insights into how breast milk odor might exert analgesic effects are grounded in neurobiological principles of sensory processing and emotional conditioning. Olfactory signals processed by the neonate’s limbic system and hypothalamic-pituitary-adrenal axis might promote calming responses and bias attention away from nociceptive inputs. Additionally, familiar and biologically salient odors related to breastfeeding may invoke a sense of safety and security, further mitigating pain perception. However, these theoretical frameworks require further confirmation through targeted neurophysiological and imaging studies in neonatal populations.
The clinical implementation of breast milk odor as a pain relief intervention offers tangible practical advantages. It is a low-cost, readily available stimulus that poses no risk of adverse side effects or systemic drug interactions. Moreover, it aligns with the ethos of family-centered care by integrating maternal biological cues into the therapeutic milieu. Nevertheless, the absence of standardized protocols detailing the precise timing, duration, and concentration of odor exposure currently limits widespread adoption within neonatal intensive care units (NICUs).
Despite promising preliminary data, Bertol et al. emphasize the urgent necessity for large-scale, high-quality randomized controlled trials expressly designed to evaluate the analgesic efficacy of breast milk odor. These future investigations should strive to harmonize methodological variables, explore dose-response relationships, and consider confounding factors such as gestational age, clinical condition, and prior pain exposure. Moreover, combining olfactory interventions with other sensory regulatory techniques or minimal pharmacological doses could yield synergistic pain relief strategies.
Pending additional evidence, clinicians are advised to interpret the current body of research with cautious optimism. While the use of breast milk odor may serve as a valuable component within a multimodal pain management framework, it is unlikely to replace established pharmacological options outright. Instead, its greatest utility may lie in augmenting analgesia and enhancing the overall care experience for fragile neonates.
The broader implications of understanding and applying nonpharmacological analgesics such as breast milk odor extend beyond neonatal pain management. They open doors to non-invasive neuromodulatory techniques capable of fostering neurodevelopmental resilience and attenuating the long-term impact of early-life stressors. Such advances resonate profoundly with contemporary precision medicine approaches, seeking tailored, individualized care grounded in developmental biology and sensory integration principles.
In conclusion, the analgesic potential of human milk odor in preterm neonates represents an exciting frontier in neonatal care research. Bertol et al.’s systematic review and meta-analysis advances the field by consolidating and critically appraising the extant literature, highlighting both promising trends and persistent uncertainties. Moving forward, a collaborative and interdisciplinary research agenda encompassing neonatology, sensory neuroscience, and clinical pharmacology will be essential to unravel the full therapeutic potential of this natural, maternal-derived intervention. The journey from bench to bedside in this domain may ultimately transform how we approach the quintessential challenge of alleviating pain in our most vulnerable patients.
Subject of Research: The analgesic effects of human breast milk odor exposure on pain management in preterm neonates.
Article Title: The analgesic effects of human milk odor in preterm neonates: a systematic review and meta-analysis.
Article References:
Bertol, A.B., Vijendra, B., Aquino Gil de Freitas, P.H. et al. The analgesic effects of human milk odor in preterm neonates: a systematic review and meta-analysis. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02432-9
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41372-025-02432-9
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