Background. In a large-scale study of feeding strategies in premature infants (early vs later initiation of enteral feeding, continuous vs bolus tube-feeding, and human milk vs formula), the feeding of human milk had more effect on the outcomes measured than any other strategy studied. Therefore, this report describes the growth, nutritional status, feeding tolerance, and health of participating premature infants who were fed fortified human milk (FHM) in comparison with those who were fed exclusively preterm formula (PF). Methods. Premature infants were assigned randomly in a balanced two-way design to early (gastrointestinal priming for 10 days) versus late initiation of feeding (total parenteral nutrition only) and continuous infusion versus intermittent bolus tube-feeding groups. The type of milk was determined by parental choice and infants to receive their mother9s milk were randomized separately from those to receive formula. The duration of the study spanned the entire hospitalization of the infant. To evaluate human milk versus formula feeding, we compared outcomes of infants fed >50 mL · kg−1 · day−1 of any human milk (averaged throughout the hospitalization) with those of infants fed exclusively PF. Growth, feeding tolerance, and health status were measured daily. Serum indices of nutritional status were measured serially, and 72-hour nutrient balance studies were conducted at 6 and 9 weeks postnatally. Results. A total of 108 infants were fed either >50 mL · kg−1 · day−1 human milk (FHM,n = 62) or exclusively PF (n = 46). Gestational age (28 ± 1 weeks each), birth weight (1.07 ± 0.17 vs 1.04 ± 0.19 kg), birth length and head circumference, and distribution among feeding strategies were similar between groups. Infants fed FHM were discharged earlier (73 ± 19 vs 88 ± 47 days) despite significantly slower rates of weight gain (22 ± 7 vs 26 ± 6 g · kg−1 · day−1), length increment (0.8 ± 0.3 vs 1.0 ± 0.3 cm · week−1), and increment in the sum of five skinfold measurements (0.86 ± 0.40 vs 1.23 ± 0.42 mm · week−1) than infants fed PF. The incidence of necrotizing enterocolitis and late-onset sepsis was less in the FHM group. Overall, there were no differences in any measure of feeding tolerance between groups. Milk intakes of infants fed FHM were significantly greater than those fed PF (180 ± 13 vs 157 ± 10 mL · kg−1 · day−1). The intakes of nitrogen and copper were higher and magnesium and zinc were lower in group FHM versus PF. Fat and energy absorption were lower and phosphorus, zinc, and copper absorption were higher in group FHM versus PF. The postnatal retention (balance) surpassed the intrauterine accretion rate of nitrogen, phosphorus, magnesium, zinc, and copper in the FHM group, and of nitrogen, magnesium, and copper in the PF group. Conclusions. Although the study does not allow a comparison of FHM with unfortified human milk, the data suggest that the unique properties of human milk promote an improved host defense and gastrointestinal function compared with the feeding of formula. The benefits of improved health (less sepsis and necrotizing enterocolitis) associated with the feeding of FHM outweighed the slower rate of growth observed, suggesting that the feeding of FHM should be promoted actively in premature infants.

Feeding strategies for premature infants: beneficial outcomes of feeding fortified human milk versus preterm formula.

Background
For term infants, human milk provides adequate nutrition to facilitate growth, as well as potential beneficial effects on immunity and the maternal-infant emotional state. However, the role of human milk in premature infants is less well defined as it contains insufficient quantities of some nutrients to meet the estimated needs of the infant. Observational studies have suggested that infants fed formula have a higher rate of growth than infants who are breast fed. However, there are potential short term and long term benefits from human milk. Commercially-produced multicomponent fortifiers provide additional nutrients to supplement human milk (in the form of protein, calcium, phosphate, and carbohydrate, as well as vitamins and trace minerals).

Objectives
The main objective was to determine if addition of multicomponent nutritional supplements to human milk leads to improved growth, bone metabolism and neurodevelopmental outcomes without significant adverse effects in premature infants.

Search methods
Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 3003), MEDLINE (searched August 29, 2003), previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language.

Selection criteria
All trials utilising random or quasi-random allocation to supplementation of human milk with multiple nutrients or no supplementation in premature infants within a nursery setting were eligible.

Data collection and analysis
Data were extracted using the standard methods of the Cochrane Collaboration and its Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference.

Main results
Supplementation of human milk with multicomponent fortifiers is associated with short term increases in weight gain, linear and head growth. There is no effect on serum alkaline phosphatase levels; it is not clear if there is an effect on bone mineral content. Nitrogen retention and blood urea levels appear to be increased.

There are insufficient data to evaluate long term neurodevelopmental and growth outcomes, although there appears to be no effect on growth beyond one year of life.

Use of multicomponent fortifiers does not appear to be associated with adverse effects, although the total number of infants studied and the large amount of missing data reduces confidence in this conclusion. Blood urea levels are increased and blood pH levels minimally decreased, but the clinical significance of this is uncertain.

Authors' conclusions
Multicomponent fortification of human milk is associated with short-term improvements in weight gain, linear and head growth. Despite the absence of evidence of long-term benefit and insufficient evidence to be reassured that there are no deleterious effects, it is unlikely that further studies evaluating fortification of human milk versus no supplementation will be performed. Further research should be directed toward comparisons between different proprietary preparations and evaluating both short-term and long-term outcomes in search of the "optimal" composition of fortifiers.

Multicomponent fortified human milk for promoting growth in preterm infants.

Background To evaluate feeding tolerance in premature infants immediately after the addition of human milk fortifier (HMF) to their expressed human milk diet. Methods Data on milk intake, feeding tolerance, and related assessments and growth milestones from a prospective study of feeding strategies in premature infants were analyzed. The database was searched for the first day HMF was added to the feeding of infants receiving human milk exclusively. The following assessments were tabulated for the 5 days before and the 5 days after the addition of HMF: milk intake, the number of episodes of abdominal distension, gastric residual volume (GRV) more than 2 ml/kg and more than 50% of the volume fed in the prior 3 hours. bile-stained gastric residual, emesis or regurgitation, blood in the stool, the number of abdominal radiographs, the number of episodes of apnea and bradycardia, changes in findings in the clinical examination, and the number of hours feeding was withheld. The time to achieve full tube feeding, complete oral feeding, and hospital discharge were recorded. Results Seventy-six exclusively human milk-fed premature infants (birth weight, 1065+/-18 g; gestational age, 27+/-0.1 weeks; mean +/- SEM) who received HMF beginning 22+/-0.8 days of age were evaluated. There were significant increases in milk intake and in the number of episodes of GRV more than 2 ml/kg and emesis after the addition of HMF. There were no differences in the number of hours feeding was withheld or any other assessment after the addition of HMF. Infants with increases in GRV more than 2 ml/kg and/or emesis after the addition of HMF were not more likely to be delayed in the time to achieve full tube feeding, complete oral feeding, or hospital discharge than infants who did not experience these events. Conclusion These data suggest that, when all feeding and related assessments and the time to achieve important growth milestones are considered, the addition of HMF does not adversely affect the outcome of the premature infant.

Feeding tolerance in premature infants fed fortified human milk.

OBJECTIVE: A nutritional audit was performed to determine whether current feeding regimes were achieving nutritional goals and to evaluate the use of breastmilk (BM) in a neonatal unit (NNU). METHODS: All fluid consumed or infused daily was documented with daily weight and weekly length and head circumference measurements in 90 preterm infants (gestational age 30.1 +/- 2.6 weeks) while in the NNU for 60 +/- 27 days. Daily protein and energy intakes were calculated using values for South Australian preterm BM. RESULTS: Parenteral nutrition provided 85% of the daily energy in week 1 falling to 11% by week 6. Ninety per cent of infants received some of their mother's BM and 62% were discharged at least partially breastfed. Protein and energy intakes were 1.03 +/- 0.35 g and 55 +/- 10 kcal/kg/day in week 1, increasing to 2.52 +/- 0.60 g and 109 +/- 15 kcal/kg per day by week 4. Protein intake correlated with weight gain (r2 = 0.39). Weight gain was 14.0 +/- 2.0 g/kg per day and z-scores for weight declined from -0.25 on admission to -1.22 on discharge, P < 0.0001. When infants were divided into two groups comprising those who received BM or formula as their predominant enteral feed, growth and protein intake (but not energy intake) were lower in the BM-fed infants. However, enteral feeds were tolerated earlier and more quickly in those infants receiving predominantly BM. CONCLUSION: Energy requirements were readily met using current feeding regimes for preterm infants but protein intakes were marginal. Mothers of preterm infants had similar breastfeeding rates to mothers of term infants in South Australia. The long-term effects of the lower growth rates of preterm infants fed predominantly BM compared with those fed predominantly formula are unknown and need be balanced against the benefits of BM.

The use of breastmilk in a neonatal unit and its relationship to protein and energy intake and growth

Human milk is often inadequate nutritionally for preterm infants. We investigated the effect of adding a commercially prepared milk fortifier to human (maternal or bank) milk and measured changes in lower leg length velocity (LLLvel) using knemometry weight gain and biochemical indices of nutrition. Babies were allocated to one of three feed groups in a semi-randomized fashion to receive human milk alone (group I) fortified human milk (group II) or a preterm formula (group III). The birthweights (median and R) and birth gestations (median and R) of the three groups were as follows: group I 1099 g (654-1248 g) and 28 wk (26-32 wk); group II 838 g (742-1340 g) and 31 wk (28-36); group III 1136 g (624-1552 g) and 32 wk (27-36 wk). All babies who received fortified milk either showed significant (p = 0. 0004) acceleration in LLLvel during the period studied or maintained their pre-study period velocity. This increase in LLLvel was comparable to that achieved by a group of babies given a standard preterm infant formula (p < 0.001). By comparison the control groups change in LLLvel was more modest (p = 0.04). Babies who received human milk with the fortifier added had the lowest serum levels of alkaline phosphatase at the end of the study period when compared to the other two groups. Other biochemical indices were similar in the three feed groups. No adverse clinical events were encountered which could be attributed to the use of the breast milk fortifier. (authors)

Changes in growth and metabolism in very low birthweight infants fed with fortified breast milk.

A preliminary investigation was made into the effectiveness of two breastmilk fortifiers on the Australian market (FM-85 [Nestle, Vevey, Switzerland] and Enfamil Human Milk Fortifier [EHMF; Mead Johnson, Evansville, IN, USA]). Infants < 1800 g and < 34 weeks gestation at birth, who were receiving breast milk, were randomized to receive either of the fortifiers (n = 14 for FM-85, n = 10 for EHMF), until a weight of 2 kg was reached. Infants not receiving breast milk (n = 9) were fed a preterm formula (Prenan, Nestle). The two fortifier groups were similar in most parameters examined: (i) weight gain (17.9 +/- 3.0 vs 17.4 +/- 3.5 g/kg per day); (ii) head circumference growth (1.02 +/- 0.28 vs 1.03 +/- 0.25 cm/week); (iii) arm muscle area growth (32.6 +/- 20.0 vs 33.5 +/- 13.7 mm2/week); (iv) arm fat area growth (14.0 +/- 8.7 mm2/week); (v) plasma calcium (2.52 +/- 0.08 vs 2.58 +/- 0.15 mmol/L); (vi) plasma phosphate (2.02 +/- 0.21 vs 2.13 +/- 0.32 mmol/L); (vii) plasma copper (5.28 +/- 2.83 vs 5.66 +/- 3.07 mumol/L); and (vii) plasma zinc (13.3 +/- 5.5 vs 15.8 +/- 9.2 mumol/L). The FM-85 group had a higher alkaline phosphatase level (355 +/- 110 vs 231 +/- 70 iu/L) than the EHMF group; however, no values were outside the normal range. The Prenan group had a higher rate of weight gain (23.6 +/- 3.3 g/kg per day) and higher arm fat area growth rate (25.2 +/- 7.6 mm2/week) than the fortifier groups while all other parameters were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

How appropriate are commercially available human milk fortifiers

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How appropriate are commercially available human milk fortifiers