Analysis of factors driving variations in neonatal parenteral nutrition over a decade: A retrospective study

BACKGROUND: Parenteral nutrition (PN) is essential for supporting preterm and critically ill neonates who are unable to tolerate adequate enteral feeds. However, PN composition remains highly variable due to differences in guidelines, institutional practices, prescriber discretion, and more. This lack of standardization contributes to inconsistent nutrient delivery and may affect clinical outcomes. A deeper understanding of the sources of variation is needed to inform efforts toward more consistent and evidence-aligned prescribing. METHODS: This retrospective study analyzed 54,464 neonatal PN prescriptions issued between 2011 and 2021 to 5052 infants. Patient demographics, prescriber identifiers, and prescription year were linked through electronic health records. Temporal trends in nutrient composition were evaluated using linear mixed-effects models, with covariate adjustment. Dimensionality reduction with t-distributed Stochastic Neighbor Embedding (t-SNE) was applied to visualize temporal clustering of prescriptions and prescriber-level similarity in dosing patterns. RESULTS: PN composition demonstrated clear temporal variability across the decade. Macronutrient shifts diminished after adjusting for patient demographics, indicating that changes were primarily driven by shifts in the NICU population. In contrast, most micronutrients retained significant year effects. Variance partitioning revealed that prescriber identity explained substantially more variability than prescription year for nearly all electrolytes. Guideline updates also shaped certain changes, such as Selenium, which shifted in line with a specific update rather than prescriber preference. CONCLUSION: Neonatal PN is influenced by multiple factors, with prescriber-level differences emerging as a dominant driver for micronutrients. These findings highlight the need for targeted standardization efforts that reduce unnecessary heterogeneity while preserving flexibility for clinical judgment.