Longitudinal changes in polyunsaturated fatty acids and their metabolites in preterm human milk during early lactation.

OBJECTIVES: Long-chain polyunsaturated fatty acids (LC-PUFAs) are integral components of cell membranes and serve as precursors of bioactive lipid mediators known as oxylipins. Although oxylipins have been identified in human milk (HM), their temporal dynamics and relationships with precursor LC-PUFAs during early lactation, particularly in preterm milk, remain under-examined. This study characterized longitudinal changes in LC-PUFAs and oxylipins in HM from Japanese mothers of moderately preterm infants during the first 3 weeks of lactation. METHODS: HM samples were collected weekly for 3 consecutive weeks from breastfeeding women who delivered infants born moderately preterm (30-34 weeks of gestation). Analyses were performed on 50 HM samples from 21 participants. Selected precursor fatty acids and their derived oxylipins were quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Despite significant declines in milk arachidonic acid (AA) and docosahexaenoic acid (DHA) concentrations over the first 3 weeks of lactation, many corresponding oxylipins remained stable or increased. All measured linoleic acid (LA)-derived oxylipins increased significantly (p < 0.01) despite constant LA concentrations. Several n-3-derived oxylipins, including α-linolenic acid (ALA)-derived 13-hydroxy-9,11,15-octadecatrienoic acid (13-HOTrE), eicosapentaenoic acid (EPA)-derived 15-hydroxyeicosapentaenoic acid (15-HEPE) and DHA-derived protectin DX also increased by Week 3. Although some selected oxylipins were positively associated with their precursor fatty acids, the temporal oxylipin trajectories were not consistently aligned with changes in precursor concentrations. CONCLUSION: These findings highlight the dynamic, pathway-specific regulation of bioactive lipid mediators in preterm HM and provide a biochemical basis for future studies investigating the potential relationship between these mediators and prematurity-related morbidity.