Adjustable fortification of human milk fed to preterm infants

In adults, as protein intake increases, so does blood urea nitrogen (BUN), unless significant protein accretion is occurring and/or hepatic function; that is urea synthetic capacity, is compromised. When protein intake is low BUN is also low, unless renal or fluid status is compromised.¹ In children, BUN changes rapidly with protein intake, assuming adequate hydration.² Indeed, protein content of the diet can be directly related to the BUN; for example, if 8% of energy is protein then the BUN will be ∼8 mg/dl in the otherwise normal infant.²

The situation has been less clear-cut in preterm infants. It takes time to establish adequate energy intakes during early life in sick immature infant,³ protein is catabolized and BUN increases, irrespective of protein intake or renal function. At the same time, urea synthetic capacity^{4, 5} and/or renal excretory^{6, 7, 8} may be limited in the immature infant. Thus, early studies suggested BUN is not a valid measure of protein intake in preterm infants.^{4, 9, 10, 11}

More recent studies, one by this group,¹² suggest otherwise in the clinically stable preterm infant.¹³ In the latter study, the relationship between nitrogen accretion and growth fed two levels of protein intake, 3.0 and 3.6 g/100 kcal, was assessed. Nitrogen intake varied widely but intake and absorption were linearly related to changes in BUN (see Figure 1).¹³ These data coupled with the findings in this study support the idea that, as in older children and adults, BUN is a valid measure protein intake in preterm infants.

Figure 1

Relationship between BUN and nitrogen intake and nitrogen absorption.

The findings of this study, therefore, have important implications for feeding preterm infants. Protein requirements are not well established in preterm infants.¹⁴ Requirements will also vary depending upon (a) nutritional status at birth; that is, AGA and SGA infant, (b) sex; that is, boys accrete more lean mass and grow faster than girls,¹⁵ (c) level of maturity; that is, protein:energy needs change with advancing gestation¹⁶ and (d) previous nutritional intake; that is, requirements for ‘recovery’ will vary.³ One formulation, therefore, is unlikely to meet the protein needs of all infants.

An additional consideration in this study is the wide variation in protein content of human milk^{17, 18, 19, 20} that is rarely measured for individual mother–infant pairs. Irrespective of whether an infant is fed human milk or a preterm formula the idea that intake is ‘tailored’ to meet individual needs and is monitored to ensure efficacy, better growth and safety is a critical concept. The Arslanoglu et al paper in the current issue demonstrates that BUN determinations are an excellent index for adequacy of protein intake. This is a commonly overlooked, but important, message for day-to-day nutritional care in the neonatal intensive care setting.