Comparative Analysis of Macronutrient and Micronutrient Composition in Human Milk from Preterm and Term Infants: Implications for Nutritional Strategies

Human milk (HM) is a dynamic and bioactive fluid that provides essential nutrients and immunological components tailored to infant developmental needs. The composition of HM varies significantly depending on gestational age, maternal nutrition, genetic background, and environmental factors. This review aims to systematically compare the macronutrient and micronutrient composition of HM from preterm and term infants, and to evaluate the implications of these differences for neonatal growth, immune function, and clinical nutrition strategies. Preterm milk differs markedly from term milk, particularly in protein quality, free amino acid content, fatty acid profile, vitamin concentrations, and immunological factors. It is enriched with α-lactalbumin, lactoferrin, sIgA, lysozyme, and medium-chain triglycerides, offering enhanced support for immune function and neurodevelopment. However, it is often lower in key nutrients such as glutamine, DHA, and minerals like iron and phosphorus, necessitating targeted fortification. Maternal dietary intake significantly affects the levels of vitamins (e.g., A, D, B12, and C) and fatty acids, while genetic polymorphisms also influence the lipid and oligosaccharide composition of HM. Understanding the compositional differences between preterm and term HM is essential for guiding individualized nutritional interventions. Clinically, fortification of preterm HM and alignment with the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), the American Academy of Pediatrics (AAP), and the World Health Organization (WHO) guidelines are critical to ensure adequate nutrient delivery and optimal neurodevelopmental outcomes. Future research should focus on the long-term effects of variable DHA and HMO levels, and the influence of maternal nutrition and genetics on milk composition.