Partially hydrolyzed formula with high sn-2 palmitic acid on eosinophils and outcomes in preterm infants: PRIOR secondary analysis.

Background: Preterm infants, with immature immune systems, are susceptible to type 2 inflammation, characterized by eosinophil recruitment, exacerbating intestinal and respiratory inflammation. Breastfeeding mitigates inflammation via sn-2 palmitic acid and immunomodulatory factors (e.g., IL-10), but formula feeding is often necessary due to clinical constraints. High sn-2 palmitic acid partially hydrolyzed formula (HPF) may reduce eosinophil-related inflammation by lowering protein immunogenicity, yet evidence is limited. Methods: This secondary analysis of the ongoing PRIOR parallel-group randomized controlled trial (ChiCTR2400093296) (evaluating formula safety and growth-related outcomes) included 90 preterm infants (gestational age <34 weeks or birth weight <2000 g), randomized to HPF (n = 45) or standard preterm formula (SPF) (n = 45) using computer-generated randomization with allocation concealment. Infants were enrolled from 1 July 2024, to 30 June 2025, and followed weekly during hospitalization and monthly after discharge until a corrected age of 3 months. Primary outcomes were hematological parameters (including eosinophil counts) at discharge; secondary outcomes included hospital stay duration, necrotizing enterocolitis (NEC) incidence, and anemia management. Generalized additive models assessed eosinophil levels relative to corrected gestational age and formula exposure duration. Results: Eighty infants completed the in-hospital phase (HPF, n = 41; SPF, n = 39). Groups were similar in gestational age, birth weight, sex, and Apgar score (all p > 0.05). HPF showed a steeper decline trend in eosinophil percentage after prolonged exposure (>25 days, p = 0.053), suggesting inflammation suppression. Hospital stay duration (HPF, 30 (17-38) days vs. SPF, 27 (20-36) days; p = 0.825) and NEC incidence (2.4% vs. 2.4%; p = 1.000) did not differ significantly. Conclusion: HPF demonstrates potential in reducing eosinophil-mediated inflammation in preterm infants but has no significant impact on hospital stay or NEC incidence. This secondary analysis supports optimizing preterm formulas and warrants further investigation into long-term immune benefits.