Abstract: Objective: To conduct comparative analysis of the dynamic trend of breast milk lipid composition across different lactation stages in mothers of preterm and term infants with the aim of providing a basis for optimizing feeding strategies for preterm neonates. Methods: From January 2023 to May 2024, nine preterm mother-infant dyads and ten term mother-infant dyads were recruited from Northwest Women’s and Children’s Hospital and two tertiary hospitals in Gansu province. Breast milk samples were collected at three time points: days 0–7 postpartum (colostrum), days 8–14 (transitional milk), and 2 months (mature milk). High-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD), liquid chromatography-tandem quadrupole mass spectrometry (LC-qMS) and gas chromatography with flame ionization detection (GC-FID) were used to quantify total fat, structural lipids, gangliosides, phospholipids, and fatty acids in breast milk. Results: The lipid composition and its dynamic changes in breast milk for preterm infants significantly differed from those in breast milk for term infants. In preterm breast milk, total phospholipids, phosphatidylcholine (PC), and phosphatidylserine (PS) levels remained stable throughout the lactation period, whereas those in term breast milk gradually decreased. Total phospholipids, PC and sphingomyelin (SM) levels in preterm colostrum, as well as SM levels in preterm transitional and mature milk were lower than their respective counterparts in term breast milk. Conversely, phosphatidylethanolamine (PE) content was higher in preterm mature milk than in its term counterpart. Fatty acid analysis revealed that eicosatrienoic acid (20:3n3) concentrations in preterm colostrum and transitional milk, as well as eicosapentaenoic acid (EPA, 20:5n3) levels in preterm transitional and mature milk were significantly lower than their counterparts in term breast milk. However, no statistically significant differences were observed between preterm and term breast milk in docosahexaenoic acid (DHA, 22:6n3) or arachidonic acid (ARA, 20:4n6) concentrations across lactation stages. Conclusion: The lipid composition of human milk for preterm infants remains relatively stable: the levels of total phospholipids, PC, and PS remain stable, likely in response to the nutritional requirements of preterm infants, while PE levels in mature milk markedly increase, which is maybe related to the neurodevelopmental requirements. Additionally, the levels of key long-chain unsaturated fatty acids (e.g., EPA) are lower in preterm than in term breast milk, underscoring the need for targeted nutritional interventions to address the specific demands during the rapid developmental phases.

Key words: breast milk lipids, fatty acids, preterm infants, docosahexaenoic acid, arachidonic acid, eicosapentaenoic acid