IV. Individualized Fortification of Human Milk

BACKGROUND The particular composition of HM makes it uniquely suited not only to term but also to preterm infants. Feeding preterm infants with HM confers protection against NEC, sepsis and other infections, decreases the risk of death, improves long-term neurocognitive development and cardiovascular health outcomes. HM is the recommended feeding for all neonates including premature infants as stated in the most recent Recommendation Papers of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the American Academy of Pediatrics (1–3). Unfortified HM provides insufficient amounts of nutrients to the VLBW infants when fed at the usual feeding volumes leading to slow growth with the potential of neurocognitive impairment and other poor health outcomes such as retinopathy and bronchopulmonary dysplasia. That is why it needs to be fortified with nutrients, particularly with protein, calcium, and phosphate to meet high requirements of this group of tiny preterm babies (4,5). Current fortification regimen in most of the NICUs is to add a fixed, recommended amount of multicomponent of HM fortifier to a certain volume of HM. Most of the available multicomponent fortifiers contain varying amounts of protein, carbohydrate/fat, calcium, phosphate, other minerals (zinc, manganese, magnesium, and copper), vitamins, and electrolytes. This practice is defined as “Standard HM Fortification” (4). Standard HM fortification, designed to optimize nutritional intakes, falls short of this goal with regard to protein. In fact in the last few years, it became evident that preterm infants fed fortified HM in standard fashion receive less protein than assumed and continue to grow slower than infants fed preterm formula (6–8). Refinement of fortification regimens was essential. Among the refinement strategies, two “Individualized Fortification” methods have been proposed: 1. Adjustable Fortification (9,10), 2.Targeted Fortification (11–13). WELL ESTABLISHED Protein is limiting for growth and neurocognitive development, and its shortfall is not acceptable. Adjustable fortification (9) has been designed to overcome the ongoing protein undernutrition despite standard fortification. It foresees extra protein supplementation in addition to standard multicomponent fortification according to each infant's need. Protein intake is adjusted on the basis of the infant's metabolic response, evaluated through periodic determinations of blood urea nitrogen (BUN). This model being proposed in 1995 (14), has undergone further improvements and in 2006 has been shown to be feasible and effective in providing the preterm infants with adequate protein intakes and appropriate growth approximating intrauterine intakes and growth. The study published in 2006 (9) is the unique randomized controlled trial showing the superiority of an individualized fortification method to standard regimen in terms of growth and protein intake. It has also been successful to improve head circumference gain during NICU stay. The model has been slightly modified in 2012 taking into consideration some observations in practice (10). Advantages Does not make any assumptions regarding an infant's protein requirements; it directly monitors the metabolic response taking into consideration the actual protein status in each infant. Avoids possible excessive protein intake. Does not need frequent milk analyses and equipment, and it is not labor intensive. Adjustable fortification regimen has been promoted also by Italian Association of Human Milk Banks (AIBLUD) and is in use in several NICUs in Italy and Turkey with success. In 2013 a slightly different form of adjustable fortification regimen replicated similar results in terms of improved in-hospital growth in VLBW infants (15). NOT YET ESTABLISHED The following studies need to be conducted: Randomized controlled trials evaluating the impact of adjustable fortification on long-term neurocognitive outcomes. Comparison of 2 individualized fortification regimens: targeted vs adjustable. Randomized controlled trials comparing the efficacy and safety of increasing the protein content in fortifiers (0.5–1 g) in a fixed manner (vs adjustable fortification). RECOMMENDATIONS Current standard fortification methods have yielded inadequate protein intakes resulting in slower growth compared to formulas. The use of individualized fortification, particularly adjustable fortification which is effective, safe and practical in reaching adequate protein intakes and growth, is recommended.