The efficiency and safety of a higher protein human milk fortifier on growth for preterm human milk-fed infants.

Abstract

Preterm births represent approximately 8% of births in Australia, and this rate has been increasing over the last decade. Nutrition is a cornerstone of their medical management, yet very premature infants remain difficult to adequately nourish and growth failure is a common consequence of prematurity. Human milk is the preferred feed but has inadequate protein to meet their high requirements and must be fortified. Commercial fortifiers contain conservative amounts of protein and fail to compensate for the fall in the protein content of expressed breast milk over time. This thesis tested the hypothesis that preterm infants fed human milk with a higher protein fortifier (1.4 g/100 mL) would have greater length gain with no metabolic disturbances when compared to infants fed human milk fortified to standard levels (1.0 g protein/100 mL). In a randomised controlled trial infants born <31 weeks gestation, whose mothers intended to provide breast milk for their infants, were randomly allocated to receive either the experimental fortifier containing 1.4 g protein or a fortifier equivalent to standard care, containing 1 g protein. The fortifiers were manufactured specifically for the study and were made isocaloric by adjusting the carbohydrate content. They were identical in appearance and mixing rates and all personnel involved in the trial were blinded to the allocation. Preterm formula was used if breast milk supply was inadequate. The intervention period was from the start of fortification to discharge or the infant’s estimated due date, whichever came first. The primary outcome was length gain (cm/week) and secondary outcomes included other growth measurements (weight and head circumference gain), biochemical markers (urea nitrogen, creatinine, albumin, pH, amino acids) and data describing their clinical course during the hospital admission. There was a slight improvement in length gain in the higher protein group but this did not reach statistical significance (mean (95% CI) 1.15 (1.10-1.19) and 1.09 (1.05-1.13) cm/week in the higher and standard groups respectively, p = 0.08). However, fewer infants were classified as small for gestational age for length at discharge in the higher protein group (49% versus 63% in the higher and standard protein groups, respectively, p = 0.04). There were no differences in weight or head circumference gain between the groups. Serum urea nitrogen concentrations and whole blood amino acid levels were higher in the higher protein group but plasma albumin, creatinine and pH were not different between groups. There were no differences in clinical outcomes such as retinopathy of prematurity, sepsis, necrotising enterocolitis, number of infants requiring surgery or length of hospital stay. A higher protein human milk fortifier appears to be well tolerated and safe to use in preterm human milk fed infants born <31 weeks gestation. The extra protein protects against a classification of small for gestational age for length at discharge and may improve length gain. Further studies directed toward comparisons between fortifiers with levels of protein >1 g/100 mL are required to determine the optimum protein concentration of fortifiers.