Human Milk–based Fortifiers in Preterm Infants – Clinical Benefits and Limitations in the Light of Current Evidence

Background: Preterm infants, particularly those with very low birth weight (VLBW) and extremely low birth weight (ELBW), have substantially increased nutritional requirements. Although human milk provides many protective benefits, it does not fully meet the nutritional needs of this population, which justifies the routine use of human milk fortifiers. Traditionally used bovine milk–based fortifiers (BMBF) have raised concerns regarding their potential association with necrotizing enterocolitis (NEC), which led to the development of human milk–based fortifiers (HMBF). Objective: This narrative review aimed to present the current state of knowledge regarding the clinical benefits and limitations of HMBF in preterm infants, with particular emphasis on NEC, sepsis, growth, and mortality. Materials and Methods: A narrative literature review was conducted including randomized controlled trials, observational studies, and systematic reviews and meta-analyses comparing HMBF and BMBF in preterm infants. The analysis focused on clinically relevant outcomes, particularly in ELBW infants and in the context of an exclusive human milk diet. Results: The reviewed studies indicate a lower incidence of NEC among infants receiving HMBF, particularly within exclusively human milk–based diets. Mortality was also reported to be lower in some cohorts, particularly among ELBW infants. Rates of late-onset sepsis and other major morbidities were generally comparable between groups. Some studies reported slower short-term weight gain with HMBF, whereas long-term growth outcomes showed no consistent differences between feeding strategies. Conclusions: Current evidence suggests that HMBF may reduce the risk of NEC and mortality in highly vulnerable preterm infants, particularly those with ELBW. Although some studies report slower short-term weight gain, randomized trials have not demonstrated clinically meaningful differences in long-term growth or body composition. Overall, the potential clinical benefits appear to outweigh these temporary differences in growth velocity.