Evaluation of liquid or powdered fortification of human milk on growth and bone mineralization status of preterm infants.

Thirty-five preterm (< 1500 g) infants were fed preterm human milk (PHM) supplemented with either powdered fortifier (PF) or liquid supplement (LS). Bone mineral content (BMC) of the distal third radius was measured by photon absorptiometry. Biochemical indices of nutritional and bone status were obtained every 2 weeks. The initial BMC for both feeding regimens were similar. BMC did not change over the study period for infants fed LS. Infants fed PF had BMC values greater than LS infants at weeks 2 and 4 of study. Only infants fed PF had BMC values that demonstrated a consistent increase. Serum total protein and phosphorus values were greater for PF infants at week 4 than LS infants. Weight, length, occipital-frontal circumference (OFC) gains, serum albumin, alkaline phosphatase, calcium, and vitamin D levels were similar in both groups. We conclude that products used to "enrich" PHM are adequate to meet the growth needs of the preterm infant. However, we found that infants fed the powdered fortified preterm human milk had higher bone mineralization than those fed the liquid supplemented human milk.     

Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier.

BACKGROUND: To improve the nutritional management of pre-term infants, a new individualized human milk fortification system based on presupplementation milk protein analyses was evaluated. METHODS: In an open, prospective, randomized multicenter study, 32 healthy preterm infants (birth weights, 920-1750 g) were enrolled at a mean of 21 days of age (range, 9-36 days) when tolerating exclusive enteral feedings of 150 ml/kg per day. All infants were fed human milk and were randomly allocated to fortification with a bovine whey protein fortifier (n = 16) or ultrafiltrated human milk protein (n = 16). All human milk was analyzed for protein content before fortification with the goal of a daily protein intake of 3.5 g/kg. During the study period (mean, 24 days) daily aliquots of the fortified milk were obtained for subsequent analyses of the protein content. RESULTS: Both fortifiers were well tolerated, and growth gain in weight, length, and head circumference, as well as final preprandial concentrations of serum urea, transthyretin, transferrin, and albumin were similar in both groups. The ultimate estimated protein intake was equivalent in both groups (mean 3.1+/-0.1 g/kg per day). Serum amino acid profiles were similar in both feeding groups, except for threonine (significantly higher in the bovine fortifier group) and proline and ornithine (significantly higher in the human milk protein group). CONCLUSIONS: Protein analyses of the milk before individual fortification provides a new tool for an individualized feeding system of the preterm infant. The bovine whey protein fortifier attained biochemical and growth results similar to those found in infants fed human milk protein exclusively with the corresponding protein intakes.     

Diet and bone mineral content at term in premature infants

Premature infants are at risk of developing metabolic bone disease mainly because of low calcium and phosphorus intake. We have examined the effect of different mineral supplements on bone mineral content at term in 127 premature infants with gestational age <32 wk in a double-blinded randomized trial. We used either phosphate supplementation of human milk as recommended by the European Society of Pediatric Gastroenterology and Nutrition or fortified supplementation with protein, calcium, and phosphorus or preterm formula as recommended by the American Academy of Pediatrics. The intervention period was from 1 week old until 36 wk of gestational age, and the infants were fed approximately 200 mL x kg(-1) x d(-1). Bone mineral content was measured at term by dual-energy x-ray absorptiometry scan. Surprisingly, neither phosphate, fortifier, nor preterm formula supplementation had any significant effect on bone mineral content at term compared with infants fed their own mother's milk only. There was a tendency to higher total bone mineral content in infants fed preterm formula compared with infants fed their own mother's milk only (p = 0.05), but when the bone mineral content was corrected for the size of the infant, there was no difference (p = 0.68). Infants fed preterm formula had a significantly higher weight at term compared with infants fed their own mother's milk only (p = 0.02), but did not differ significantly in length or head circumference. In a regression analysis, the amount of supplemented phosphorus was significantly associated with weight at term (p = 0.008). We conclude that when feeding 200 mL x kg(-1) x d(-1), mineral supplementation of human milk or use of preterm formula does not significantly improve bone mineralization outcome at term.     

Serum phenylalanine in preterm newborns fed different diets of human milk

ObjectiveTo evaluate phenylalanine plasma profile in preterm newborns fed different human milk diets.MethodsTwenty-four very-low weight preterm newborns were distributed randomly in three groups with different feeding types: Group I: banked human milk plus 5% commercial fortifier with bovine protein, Group II: banked human milk plus evaporated fortifier derived from modified human milk, Group III: banked human milk plus lyophilized fortifier derived from modified human milk. The newborns received the group diet when full diet was attained at 15 ± 2 days. Plasma amino acid analysis was performedon the first and last day of feeding. Comparison among groups was performed by statistical tests: one way ANOVA with Tukey's post-test using SPSS software, version 20.0 (IBM Corp, NY, USA), considering a significance level of 5%.ResultsPhenylalanine levels in the first and second analysis were, respectively, in Group I: 11.9 ± 1.22 and 29.72 ± 0.73; in Group II: 11.72 ± 1.04 and 13.44 ± 0.61; and in Group III: 11.3 ± 1.18 and 15.42 ± 0.83 μmol/L.ConclusionThe observed results demonstrated that human milk with fortifiers derived from human milk acted as a good substratum for preterm infant feeding both in the evaporated or the lyophilized form, without significant increases in plasma phenylalanine levels in comparison to human milk with commercial fortifier.     

The use of human milk for premature infants

Various methods have been reported and used clinically to augment the nutrient supply for human milk-fed premature infants. These methods include specialized maltinutrient powdered mixtures (fortifiers), complete liquid formulas designed to be mixed with human milk, complete powdered formulas to be mixed with human milk, and alternate feeding of human milk and preterm formula. Although the optimum nutrition of premature infants is unknown, data are accumulating to suggest that human milk, fortified with additional nutrients, is appropriate for tube-fed infants. The use of fortified human milk typically provides premature infants adequate growth, nutrient retention, and biochemical indices of nutritional status when fed at approximately 180 mL/kg/d compared with unfortified human milk. Data are needed to determine the precise quantity of nutrients to be added as supplements. Nutrient interactions have not been explored in detail. Although large quantities of calcium seem to be needed, the exogenous calcium may affect fat absorption adversely. Manipulation of milk may affect the intrinsic host-defense properties of the milk. Compared with preterm formula, the feeding of fortified human milk may provide significant protection from infection and NEC. Lastly, the potential stimulation of an enteromammary pathway through skin-to-skin contact provides species-specific antimicrobial protection for premature infants. Several of these areas require additional exploration. Thus, for premature infants, neonatal centers should encourage the feeding of fortified human milk, together with skin-to-skin contact, as reasonable methods to enhance milk production while potentially facilitating the development of an enteromammary response.     

Nitrogen and fat balances in very low birth weight infants fed human milk fortified with human milk or bovine milk protein

The study was designed to compare two different human milk fortifiers in a group of very low birth weight (VLBW) infants by analysing nitrogen and fat balances, serum concentrations of alpha-amino-nitrogen, urea, and prealbumin as well as growth rates when human milk enriched with one of the two studied fortifiers was fed to the infants. Fortifier A contained different bovine proteins, peptides and amino acids and had an amino acid composition comparable to that of the nutritional available proteins in human milk, with carbohydrates, and minerals. Fortifier B was composed of freeze-dried skimmed human milk and minerals to achieve a similar macronutrient composition in both fortifiers.Eleven infants were fed with human milk enriched with fortifier A and 13 with fortifier B. After a 10-day equilibration period, a 3-day metabolic balance was performed. On the 14th day of the study blood was obtained preprandially for serum analysis and growth rates were estimated. The nitrogen absorption rate (93.8% vs 93.5%) as well as the retention rate (80.8% vs 78.5%) were no different between the groups. The fat absorption rate (92.3% vs 91.5%) as well as the weight gain (32.1 vs 31.1 g/day) were similar and there were no differences in the serum parameters studied. The results indicate that feeding VLBW infants with human milk enriched with a well-balanced bovine fortifier fulfil their nutritional requirements as well as diets composed exclusively of human milk protein.     

Bone mineralization in preterm infants fed human milk with and without mineral supplementation

The bone mineral status of healthy preterm infants fed maternal milk was compared with that of similar infants fed maternal milk with mineral supplementation. Fifty infants with birth weight less than 1600 g were fed human milk for 1 week until reaching an intake of 120 kcal/kg/d. Thereafter, infants were assigned randomly to one of three diets: (1) continued unsupplemented human milk, providing an intake of 40 to 50 mg/kg/d calcium and 23 to 30 mg/kg/d phosphorus; (2) human milk mixed with a high mineral containing formula, providing total intakes of 130 mg/kg/d calcium and 68 mg/kg/d phosphorus; or (3) human milk alone for 1 additional week, followed by human milk mixed with a powdered fortifier, providing total intakes of 160 mg/kg/d calcium and 90 mg/kg/d phosphorus. Infants fed human milk with formula supplementation, but not those fed human milk with fortifier, had significantly higher serum phosphorus concentrations and significantly lower serum alkaline phosphatase concentrations than did those fed unsupplemented human milk (P less than 0.01). Bone mineral content of the humerus, determined by photon absorptiometry, however, was similar in all three groups; values averaged 0.104 g/cm at the beginning of the study, and remained unchanged irrespective of mineral supplementation. Shortly before hospital discharge, study diets were discontinued and infants were fed standard proprietary formula or were nursed by their mothers. At 44 weeks postconceptional age (7 to 10 weeks after change in diet), infants were reexamined. Serum phosphorus concentrations increased, serum alkaline phosphatase concentrations decreased, and bone mineral content more than doubled to values comparable with those in term infants. Results at follow-up were comparable for all three initial diet groups and for infants who were formula-fed or breast-fed after hospital discharge. The lack of any significant effect of early maternal milk supplementation on bone mineralization by 44 weeks postconceptional age suggests that these methods of supplementation of maternal milk may not be warranted for healthy preterm infants.     

Oligosaccharides might stimulate calcium absorption in formula-fed preterm infants

Among other components of human milk, oligosaccharides might contribute to the high efficiency of calcium absorption of breastfed infants. In adults, it can be shown that dietary oligosaccharides can improve calcium absorption. The present analysis was performed to evaluate a possible influence of dietary oligosaccharides on parameters of calcium metabolism in preterm infants. The concentrations of calcium and phosphorus in plasma and in spot urine samples as well as the plasma activity of the alkaline phosphatase were measured in preterm infants fed either a standard formula (n = 15) or a formula supplemented with dietary oligosaccharides (n = 15) at the end of a 4-wk feeding period. CONCLUSIONS: There was no influence of the different diets on the plasma concentration of calcium and phosphorus or on the plasma activity of alkaline phosphatase. In urine, there was a tendency towards higher calcium concentrations in the group fed the supplemented formula compared concentrations in the group fed the standard formula. The concentrations of phosphate were not significantly different and, as a consequence, there was a tendency towards a higher Ca/P molar ratio in the group fed the supplemented formula. The data indicate that the calcium absorption might be influenced by the dietary oligosaccharides. Thus, the possible effect of dietary oligosaccharides on calcium homeostasis should be included in the discussion concerning the consequences of the use of dietary oligosaccharides in preterm infant nutrition.     

Oligosaccharides might stimulate calcium absorption in formula-fed preterm infants

Among other components of human milk, oligosaccharides might contribute to the high efficiency of calcium absorption of breastfed infants. In adults, it can be shown that dietary oligosaccharides can improve calcium absorption. The present analysis was performed to evaluate a possible influence of dietary oligosaccharides on parameters of calcium metabolism in preterm infants. The concentrations of calcium and phosphorus in plasma and in spot urine samples as well as the plasma activity of the alkaline phosphatase were measured in preterm infants fed either a standard formula ( n = 15) or a formula supplemented with dietary oligosaccharides ( n = 15) at the end of a 4-wk feeding period.
Conclusions : There was no influence of the different diets on the plasma concentration of calcium and phosphorus or on the plasma activity of alkaline phosphatase. In urine, there was a tendency towards higher calcium concentrations in the group fed the supplemented formula compared concentrations in the group fed the standard formula. The concentrations of phosphate were not significantly different and, as a consequence, there was a tendency towards a higher Ca/P molar ratio in the group fed the supplemented formula. The data indicate that the calcium absorption might be influenced by the dietary oligosaccharides. Thus, the possible effect of dietary oligosaccharides on calcium homeostasis should be included in the discussion concerning the consequences of the use of dietary oligosaccharides in preterm infant nutrition.     

Human milk supplementation for preterm infants

Nutrition support of the premature infant must be designed to compensate for metabolic and gastrointestinal immaturity, immunologic compromise, and associated medical conditions. The beneficial effects of human milk extend to the feeding of premature infants. However, nutritional concerns arise because the quantity of nutrients in human milk may not meet the great nutrient needs of the premature infant born weighing less than 1500 g. Human milk fortifiers are available to provide optimum nutrition. This review summarizes the benefits and limitations of human milk for the premature infant.     

Human milk supplementation for preterm infants

Nutrition support of the premature infant must be designed to compensate for metabolic and gastrointestinal immaturity, immunologic compromise, and associated medical conditions. The beneficial effects of human milk extend to the feeding of premature infants. However, nutritional concerns arise because the quantity of nutrients in human milk may not meet the great nutrient needs of the premature infant born weighing less than 1500 g. Human milk fortifiers are available to provide optimum nutrition. This review summarizes the benefits and limitations of human milk for the premature infant.     

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age.

BACKGROUND: The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS: In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS: Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS: The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.     

Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method

BACKGROUND: Data on enteral feeding management of premature infants are limited and often not the subject of randomized clinical trials. Several small studies suggest benefits from the early initiation of feeding, but do not assess the combined effects of time of initiation of feeding, tube-feeding method, and type of milk used. Either singly or in combination, these treatments may affect growth, bone mineralization, biochemical measures of nutritional status, and feeding tolerance, and, ultimately, the duration of hospitalization. METHODS: A total of 171 premature infants, stratified by gestational age (26 to 30 weeks) and diet (human milk or preterm formula) were assigned randomly among four treatment combinations in a balanced two-way design comparing the presence or absence of gastrointestinal (GI) priming for 10 days and continuous infusion versus intermittent bolus tube-feeding. RESULTS: The major outcome, time required for infants to attain full oral feeding, was similar among treatments. GI priming was not associated with any measured adverse effect and was associated with better calcium and phosphorus retention, higher serum calcium and alkaline phosphatase activity, and shorter intestinal transit times. The bolus tube-feeding method was associated with significantly less feeding intolerance and greater rate of weight gain than the continuous method. In addition, the greater the quantity of human milk fed, the lower the morbidity. CONCLUSIONS: Early GI priming with human milk, using the bolus tube-feeding method, may provide the best advantage for the premature infant.     

Choice of formula and human milk supplement for preterm infants in Australia

Human milk (HM) is considered to be the optimal feed of choice for neonates, however, for preterm infants, HM fortifiers are often added to increase growth. If HM is unavailable, preterm formula is the next best option for preterm infants. Choosing which fortifier, if any, to use or which formula can be confusing. In this paper, the composition of milk feeds available in Australia and New Zealand is reviewed with the aim of assisting paediatricians to decide which feed is most appropriate for their patients.     

Fat-soluble vitamin supplements for enterally fed preterm infants

Fat-soluble vitamin requirements for the enterally fed premature infant are an important concern, both before and after discharge from the neonatal intensive care unit. Because preterm infants fed unsupplemented human milk receive deficient quantities of these vitamins (A, D, E, and K), supplements are very important for this population. Vitamin intakes with special formulas for low birth weight infants and human milk fortifiers are also reviewed.     

Enteral feeding in the preterm infant

In planning enteral feeding in the preterm infant, decisions need to be made regarding the feeding schedule, choice of milk, and the route of administration. Feeds should be commenced within a week after birth beginning with subnutritional quantities. Preterm human milk from the infant's own mother is the milk of choice. When full enteral feeding is established, supplementation with human milk fortifier is recommended. Donor human milk and preterm formula are alternatives. Early establishment of enteral nutrition and maintenance of optimal nutrition during infancy are important as dietary manipulations in preterm infants have potential long-term influences on their health, growth and neurodevelopment.     

Enteral nutrition for premature infants: the role of human milk

Nutrition support of the premature infant must be designed to compensate for metabolic and gastrointestinal immaturity, immunologic insufficiency, and the demands of associated medical conditions. The beneficial effects of human milk extend to the feeding of premature infants. Although human milk enhances immunity, nutritional concerns arise because the milk might not meet the expanded nutrient requirements of very low birth weight premature infants. Human milk fortifiers are available to provide optimum nutrition. This chapter summarizes the benefits and limitations of human milk for the premature infant.     

Measurement of bone mineral density by dual energy X-ray absorptiometry in preterm infants fed human milk or formula

Bone mineralization of healthy preterm infants fed human milk were compared with that of similar fed preterm formula. Bone mineralization was studied by dual energy X-ray absorptiometry in 43 preterm infants divided into two groups; 21 preterm infants were fed with maternal breast milk and 22 preterm infants with a preterm formula containing 70 mg calcium and 35 mg phosphorus per decilitre. Conclusion Preterm infants fed breast milk had lower bone mineral density than the preterm formula-fed group. Fortifying preterm human milk with calcium and phosphorus will improve bone mineralization in preterm infants. Received: 26 November 1996 and in revised form: 26 August 1997 / Accepted: 9 September 1997     

Feeding preterm infants after hospital discharge: a commentary by the ESPGHAN Committee on Nutrition

Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding.     

Macromineral balances in premature infants fed their own mothers' milk or formula

The premature infant's own mother's milk (preterm milk) and modified infant formula (SMA, 67 and 80 kcal/dl) were fed to paired groups of seven infants, all of whom were of very low birth weight (VLBW) (less than 1.3 kg) and were studied during the first month of life. Sodium, potassium, magnesium, calcium, and phosphorus status was compared. The apparent retention of sodium from their mother's milk paralleled intrauterine retention rates and was greater than retention from SMA formula (P less than 0.01) during the first two weeks of life. However, when the formula was supplemented with NaHCO3 to intakes of 2.7 mmol Na/kg/24 hr after week 2, the infants retained adequate amounts of sodium. Potassium retention was similar to intrauterine retention rates in both groups throughout the four postnatal weeks. Magnesium intake, but not retention, was consistently higher in the group fed SMA (P less than 0.01), and intrauterine retention rates were achieved only in the group given formula. Calcium and phosphorus intakes from SMA were also higher (P less than 0.01) than from human milk. However, retention of calcium and phosphorus in both groups did not meet intrauterine retention rates, and hypophosphatemia developed in infants who received their mothers' milk. Growth in length and head circumference in both groups approximated intrauterine growth rates. If it is assumed that body composition of the growing VLBW infants should be similar to the composition of the fetus at corresponding gestational ages, then their nutrient requirements should be based on knowledge of intrauterine nutrient accretion rates. Based on this premise, we conclude that, for the growing VLBW infant, early maternal milk provided for sufficient retention of sodium, chloride, and potassium during the first four postnatal weeks. Neither human preterm milk nor SMA supplied adequate calcium and phosphorus for the growing VLBW infant.