The effect of higher protein human milk fortifier on growth in preterm infants.

Preterm infants are difficult to adequately nourish due to their immature organ systems and prematurity related illnesses. Human milk is accepted as the preferred feed for the preterm infant but needs to be supplemented with protein, carbohydrate, vitamins and minerals to meet the metabolic needs of the infant. Currently available commercial fortifiers do not meet the recommended protein intakes suggested in the literature. This thesis tested the hypothesis that preterm infants fed a human milk fortifier with a protein content of 1.8 grams protein per 100 ml expressed breast milk would experience greater weight gain than infants fed the current nursery practice amount – 1.0 grams protein per 100 ml expressed breast milk. Criteria for eligibility of infants in this study were birth at 28–32 weeks gestation and a planned breast milk diet. Power analysis indicated that to detect a clinically significant weight gain increase of 3.31 grams per day, 60 infants in total would be required. After parental consent was obtained, 60 infants were randomised into the study between February 2012 and February 2013, with 31 in the High protein group and 29 in the Standard group. Multiple births were randomised as individual infants. Infants in the High protein group received a human milk fortifier (FM-85, Nestle) enriched with Protifar (Nutricia) which provided 1.8 grams protein per 100 ml expressed breast milk. Infants in the Standard group received a human milk fortifier (FM-85) that was equivalent to standard care and provided 1 gram protein per 100 ml expressed breast milk. The Standard diet was made isocaloric to the High Protein by the addition of carbohydrate (PolyJoule, Nutricia). The study period for infants began at randomisation and ceased when the naso-gastric tube was removed. Infants were weighed daily by care staff and weekly by trained research personnel. Length and head circumference – important measures of growth – were assessed weekly. Lean mass gain, which is better associated with adult metabolic health outcomes than adipose tissue gain in the in-hospital period, was also assessed weekly. Blood and urine chemistry markers were assessed weekly and every two weeks, respectively, as an assessment of protein nutritional status. A weekly sample of breast milk was collected if supply was abundant. Lean mass was assessed using Bioelectrical Impedance Spectroscopy, which was validated for use in preterm infants as part of this thesis. Breast milk was assessed for protein content to ensure that intake calculations were based on true, not assumed values. There were no differences in the primary outcome of weight gain or the secondary outcomes of length gain, head circumference gain or small for gestational age at discharge status. There was a significant trend for increased lean mass as a percentage of body weight in the high protein infants (p=0.03). Blood urea nitrogen and urine urea measurements were significantly higher in the High protein infants. Base excess measurements were significantly decreased in High protein infants however no infants experienced metabolic acidosis. Increasing the protein content of human milk fortifier to 1.8 grams protein did not increase weigh gain, length gain or head circumference gain in preterm infants born at 28–32 weeks gestation. While the intervention was well tolerated it is the conclusion of this thesis that the protein content of human milk fortifier does not need to be increased to 1.8 grams protein per 100 ml expressed breast milk. Further studies are required to determine the optimal macronutrient content of human milk fortifier to improve preterm growth.Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 201