Skin Barrier Modulation and Survival-Relevant Outcomes: A Systematic Review of Topical Emollients in Preterm Infants

Preterm neonates have an immature skin barrier that predisposes them to excessive water loss, microbial colonization, and systemic infection. Topical emollient therapy has been proposed as a low-cost strategy to support barrier function. However, the extent to which clinical benefits reflect direct permeability changes versus downstream biological effects remains unclear. A systematic review was conducted in accordance with PRISMA 2020. PubMed, the Cochrane Library, and Google Scholar were searched from inception to January 31, 2025. Randomized or quasi-randomized controlled trials evaluating topical emollients in preterm neonates and reporting direct or proxy skin barrier-related outcomes were included. Due to substantial heterogeneity, results were synthesized narratively following the Synthesis Without Meta-analysis (SWiM) framework. Risk of bias was assessed using Risk of Bias Tool 2 (ROB-2), and certainty of evidence was evaluated using GRADE. Seven randomized studies met the inclusion criteria. Only one preterm trial directly measured transepidermal water loss (TEWL) and demonstrated a significant reduction with coconut oil. Three trials reported improved neonatal skin condition scores (NSCS) with emollient therapy. Proxy outcomes included reduced skin deterioration, altered microbial profiles, and lower rates of culture-proven sepsis. A reduction in neonatal mortality was observed in one large trial conducted in a low-resource hospital setting. Heterogeneity in populations, emollient formulations, and outcome measures precluded quantitative meta-analysis. Overall certainty of evidence ranged from low to moderate. Topical emollients are associated with improved skin condition and selected clinical outcomes in preterm neonates, despite limited direct evidence of barrier permeability modification. Observed clinical benefits appear context-dependent and are largely driven by a single large trial. Multidimensional trials integrating biophysical, microbiological, and clinical outcomes are needed to clarify mechanisms and guide targeted clinical application.