Clinical Outcomes of Intranasal Breast Milk Administration in Preterm Infants: A Systematic Review

Introduction Intraventricular hemorrhage (IVH) is a major cause of brain injury and adverse neurodevelopmental outcomes in preterm infants. Intranasal breast milk administration has emerged as a potential neuroprotective therapy due to the bioactive and stem cell components of breast milk. This systematic review evaluated the clinical outcomes in preterm infants. Methods A systematic search of PubMed, Embase via Ovid, Cochrane Library, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform was conducted to identify studies evaluating intranasal breast milk administration in preterm infants. Primary outcomes included IVH progression and brain injury outcomes, while secondary outcomes comprised neurodevelopmental, physiological, and safety measures. Risk of bias was assessed using the RoB 2 and ROBINS-I tools. Results Five studies involving 167 preterm infants were included. Intranasal breast milk administration was associated with improved IVH-related outcomes, cerebral oxygenation, respiratory stability, and selected neurodevelopmental measures in some studies. However, findings were heterogeneous, and one study reported a higher incidence of periventricular leukomalacia after adjustment analysis. Overall, the intervention appeared feasible and well tolerated without major adverse events, although the certainty of evidence was low. Conclusion Current evidence suggests that intranasal breast milk administration is feasible in preterm infants and may have potential clinical benefits. However, the available evidence remains limited, heterogeneous, and of low certainty, precluding definitive conclusions regarding efficacy or safety. Further adequately powered studies are required to clarify its therapeutic role in neonatal care.