Inside human milk fortifiers: composition and clinical rationale

Abstract

Human milk (HM) represents the gold standard for infant’s nutrition, including preterm and very low birth weight (VLBW) infants, owing to its well-documented benefits in reducing neonatal morbidity and supporting long-term neurodevelopmental and metabolic outcomes. However, HM alone does not meet the nutritional requirements of VLBW infants as defined by current European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines, making fortification with protein, energy, and micronutrients a widely adopted strategy in Neonatal Intensive Care Units.

This article reviews the quantitative and qualitative aspects of HM fortification, with a focus on fortifiers currently available in Italy.

From a quantitative standpoint, multicomponent fortifiers provide additional protein and carbohydrates within recommended osmolality limits, though evidence on optimal protein intake thresholds and fortification strategies remains inconclusive. Lipid supplementation, particularly with docosahexaenoic acid and arachidonic acid, is recommended to increase the caloric intake, to address long-chain polyunsaturated fatty acid deficiency and to support neurodevelopment.

Regarding qualitative aspects, bovine milk-derived fortifiers remain the standard of care despite the fact that exposure to bovine milk-derived products is not optimal with respect to tolerance and the reduction of the risk of necrotizing enterocolitis. HM-derived fortifiers, despite their theoretical advantages, have not demonstrated clear superiority over bovine milk-derived products in terms of morbidity or growth outcomes, and raise significant ethical and economic concerns. Donkey milk-derived fortifiers represent an emerging and promising alternative, given their compositional similarity to HM, hypoallergenic properties, and preliminary clinical evidence showing improved feeding tolerance with comparable auxological and neurodevelopmental outcomes in VLBW infants.

Future perspectives point toward the industrial development of donkey milk-based fortifiers as a clinically feasible and ethically sustainable alternative to current bovine milk-derived formulations.