Executive summary: evaluation of the evidence to support practice guidelines for nutritional care of preterm infants-the Pre-B Project.

Preterm birth (infants born at <37 wk of gestational age) is a significant clinical and public health challenge in the United States and globally. No universally accepted practice guidelines exist for the nutritional care of preterm infants. To address the current state of knowledge and to support systematic reviews that will be used to develop evidence-informed guidance, a consortium consisting of the American Academy of Pediatrics, the ASN, the American Society for Parenteral and Enteral Nutrition, the Academy of Nutrition and Dietetics, the Food and Drug Administration, the CDC, the USDA/Agricultural Research Service (USDA/ARS), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH initiated the Pre-B Project. The project included the constitution of 4 thematic working groups charged with the following tasks: 1) develop a series of topics/questions for which there is sufficient evidence to support a systematic review process to be conducted by the Academy of Nutrition and Dietetics' Evidence Analysis Library (EAL), leading to the development of new guidelines for nutritional care of preterm infants, and 2) develop a targeted research agenda to address priority gaps in our understanding of the role of nutrition in the health and development of preterm/neonatal intensive care unit infants. This review consists of a project overview including a summary of a workshop hosted by the USDA/ARS Children's Nutrition Research Center and summary reports of the 4 working groups established to address the following themes: 1) nutrient specifications, 2) clinical/practical issues in enteral feeding, 3) gastrointestinal and surgical issues, and 4) current standards for assessing infant feeding outcomes. These reports will serve as the basis for the ultimate guideline development process to be conducted by the Academy of Nutrition and Dietetics' EAL.

An Opinion on "Staging" of Infant Formula: A Developmental Perspective on Infant Feeding.

Breast milk is a dynamic fluid with compositional changes occurring throughout the period of lactation. Some of these changes in nutrient concentrations reflect the successively slowing growth rate and developmental changes in metabolic requirements that infants undergo during the first year of life. Infant formula, in contrast, has a static composition, intended to meet the nutritional requirements of infants from birth to 6 or 12 months of age. To better fit the metabolic needs of infants and to avoid nutrient limitations or excesses, we suggest that infant formulas should change in composition with the age of the infant, that is, different formulas are created/used for different ages during the first year of life. We propose that specific formulas for 0 to 3 months (stage 1), 3 to 6 months (stage 2), and 6 to 12 months (stage 3) of age may be nutritionally and physiologically advantageous to infants. Although this initially may impose some difficult practical/conceptual issues, we believe that this staging concept would improve nutrition of formula-fed infants and, ultimately, improve outcomes and make their performance more similar to that of breast-fed infants.

Reference values of amino acids and of common clinical chemistry in plasma of healthy infants aged 1 and 4 months.

OBJECTIVE: To compare plasma levels of amino acids and clinical chemistry parameters in healthy infants at 1 and 4 months of age and to establish corresponding reference limits. METHODS: Data of three multicenter studies assessing the safety of new infant formulas were used. During these studies infants of both age-groups were either breast-fed or received formulas of low or high protein content. All samples were analyzed centrally in the same accredited laboratory. RESULTS: Plasma was collected from 521 infants in total, 157 boys and 135 girls aged 1 month and 121 boys and 108 girls aged 4 months. At the age of 1 month, 62 infants had received exclusively breast milk, 198 exclusively formula, and 27 both; in the 4-months age group corresponding numbers were 49, 158 and 18, respectively; for 9 infants, diet was unknown. Concentrations of most amino acids and clinical chemistry parameters differed significantly between both ages. Regardless of age, most plasma amino acid levels were comparable or lower in breast-fed than in formula-fed infants whereas at 1 month of age most clinical chemistry parameters were higher. While in breast-fed infants the plasma urea concentration decreased over 4 months of age, it increased in formula-fed infants. There were significant differences between infants fed a low and high protein formula. At both ages, high protein formulas resulted in significantly higher threonine, 2-aminobutyrate, and urea concentrations. CONCLUSIONS: For clinical use, age- and diet specific reference limits in infants are warranted.

The Nutritional Value of Protein-hydrolyzed Formulae.

Allergy to cow's milk proteins is a challenging condition in early infancy. Allergic infants may be predisposed to impairments of growth from either the disease itself or the nutritional constraints of the exclusion diet they should follow. Formulae based on extensively hydrolyzed cow's milk proteins are widely used, representing therapy, and constituting 100% nutrient source in the first four to six months of life and half the daily nutrient intake in the second semester of life. In some cases, these products are used also for preventive purposes. Some impairments in growth have been reported for infants using these products, even if mostly limited to the first year of life, with no apparent consequences in either the medium or long term. The macronutrient content of infant formulae based on protein hydrolysates, whichever the source, should carefully be tested not only as far as the optimal utilization of nitrogenous sources but also on the nature and metabolic fate of non-nitrogen caloric sources, represented by carbohydrates and fats, and micronutrients, particularly iron. It is recommended that studies aimed at the allergologic effects of these products also include an appropriate nutritional evaluation to determine their efficiency.

Effects of cow milk versus extensive protein hydrolysate formulas on infant cognitive development.

UNLABELLED: Little research has focused on infant developmental effects, other than growth, of formulas that differ substantially in the form of protein. To examine development of infants fed formulas differing in free amino acid content, we randomized 0.5-month-old infants (n = 79) to either a control group who fed only cow milk formula (CMF) during the first 8 months (CMF8), or to one of two experimental groups: one experimental group fed extensively protein hydrolyzed formula (EHF) for 1-3 months during first 4.5 months (EHF1-3) of life, and the other fed EHF for 8 months (EHF8). The Mullen Scales of Early Learning were administered monthly from 1.5 to 8.5 months to assess fine (FM) and gross (GM) motor control, receptive (RL) and expressive (EL) language, visual reception (VR), and an early learning composite (ELC). Across the 5.5-8.5-month time period, when compared to CMF8 infants, GM scores in EHF1-3 infants averaged 1.5 points higher (95 % CI 0.1, 3.0) and in EHF8 infants 2.2 points higher (95 % CI 0.3, 4.0). Similarly, VR scores averaged 1.9 points higher (95 % CI 0.1, 3.8) in EHF1-3 infants and 2.2 points higher (95 % CI -0.2, 4.5) in EHF8 infants. EHF8 infants' RL scores averaged 1.8 points lower (95 % CI 0.1, 3.6) than CMF8 infants. These data suggest that the form of protein in infant formula may impact cognitive development and that the higher free amino acid content in breast milk may be a contributing factor to the differential cognitive development between breastfed and CMF-fed infants. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT00994747.

Factors Determining Optimal Fatty Acid Absorption in Preterm Infants.

OBJECTIVES: The aim of the present study was to quantify absorption coefficients of specific fatty acids in preterm infants as a function of diet, formula or breast milk (BM), and postnatal age; to identify the fatty acid structural characteristics that determine optimal fatty acid absorption. METHODS: Fatty acids from dietary and fecal samples were extracted and quantified by gas chromatography-mass spectroscopy. Fatty acid absorption coefficients (FA-CFAs) were calculated by comparing the total amount of fatty acids supplied by the diet to the amount quantified in the total fecal output during a 3-day period. RESULTS: A total of 18 infants (BM 8, formula 10) were studied at 2 weeks of age, and 20 infants (BM 10, formula 10) were studied at 6 weeks of age. FA-CFAs decreased with increasing carbon length in formula-fed infants at 2 and 6 weeks. Results were similar but less in magnitude in BM-fed infants at 2 weeks with no difference at 6 weeks. CONCLUSIONS: Preterm infants fed formula demonstrated lower FA-CFAs as a function of increasing carbon length. This is consistent with limited pancreatic lipase production and with lipase being present in BM but not in formula. The fact that this pattern was seen in BM-fed infants at 2 weeks but not 6 weeks of age suggests that intestinal immaturity may also play a role in impaired fatty acid absorption. These data highlight principles that need to be considered to optimize delivery and absorption of dietary long-chain polyunsaturated fatty acids in preterm infants.

Effect of processing on polyamine content and bioactive peptides released after in vitro gastrointestinal digestion of infant formulas.

This study examined the influence of processing on polyamines and peptide release after the digestion of a commercial infant formula designed for children during the first months of life. Polyamine oxidase activity was not suppressed during the manufacturing process, which implicates that polyamine concentrations were reduced over time and during infant formula self-life. In gel electrophoresis, in vitro gastrointestinal digestion of samples with reduced amount of enzymes and time of digestion shows an increase in protein digestibility, reflected in the increase in nonprotein nitrogen after digestion and the disappearance of ß-lactoglobulin and α-lactalbumin bands in gel electrophoresis. Depending on the sample, between 22 and 87 peptides were identified after gastrointestinal digestion. A peptide from ß-casein f(98-105) with the sequence VKEAMAPK and antioxidant activity appeared in all of the samples. Other peptides with antioxidant, immunomodulatory, and antimicrobial activities were frequently found, which could have an effect on infant health. The present study confirms that the infant formula manufacturing process determines the polyamine content and peptidic profile after digestion of the infant formula. Because compositional dissimilarity between human milk and infant formula in polyamines and proteins could be responsible for some of the differences in health reported between breast-fed and formula-fed children, these changes must be taken into consideration because they may have a great effect on infant nutrition and development.

[Effect of Lactobacillus acidophilus on metabolizing lactic acid in formula milk: a quantitative analysis of the effect of erythritol].

OBJECTIVE: To evaluate the lactic acid productivity of Lactobacillus acidophilus (La) exposed to formula milk containing different concentration of erythritol. METHODS: La was cultured under anaerobic condition (80% N(2), 10% CO(2), 10% H(2)) at 37 °C in five experimental groups (formula milk mixed with different concentrations of erythritol). The five experimental groups contained 1%, 2%, 4%, 6%, and 8% erythritol, respectively (groups 1% E-M, 2% E-M, 4% E-M, 6% E-M, 8% E-M). Formula milk served as control group (group M). The lactic acid was analyzed by high performance liquid chromatography (HPLC) at 4 h intervals during 24 h. The peak-area of lactic acid was recorded and used to calculate the concentration of lactic acid through the equation of a standard curve (y = 590 244x + 67 507). ANOVA and Tukey HDS analysis were used to analyze the data. RESULTS: The concentration of lactic acid at 24 h was group M [(4.693 ± 0.105) g/L], group 1% E-M[(4.114 ± 0.186) g/L], group 2% E-M[(3.720 ± 0.158) g/L], group 4% E-M[(3.045 ± 0.152) g/L], group 6% E-M[(2.971 ± 0.086) g/L], group 8% E-M[(2.789 ± 0.142) g/L]. Statistically significant differences in lactic acid concentrations were found between different time points (P < 0.05) and between different groups (F = 187.448, P < 0.05). Moreover, the concentrations of lactic acid in each experimental group was lower than that in control group (P < 0.05). The difference among groups 4% E-M, 6% E-M, and 8% E-M were not statistically significant (P > 0.05). CONCLUSIONS: Erythritol showed the inhibition potential against La in metabolizing lactic acid in formula milk. The effect of erythritol was concentration depended. The higher concentration of erythritol contained in the milk, the better the inhibition potential against La in metabolizing lactic acid.

Sterol Composition in Infant Formulas and Estimated Intake.

Sterol contents in infant formulas (IFs) from the European market were determined, and their intakes by infants between 0 and 6 months were evaluated. Total animal sterols (mg/100 mL) ranged from 1.71 to 5.46, cholesterol being the main animal sterol (1.46-5.1). In general, cholesterol and desmosterol were lower than the human milk (HM) values indicated by other authors. Total plant sterol (mg/100 mL) ranged from 3.1 to 5.0. ß-Sitosterol, the most abundant phytosterol, ranged from 1.82 to 3.01, followed by campesterol (0.72-1.15), stigmasterol (0.27-0.53), and brassicasterol (0.14-0.28). Cholesterol intake (mg/day) ranged from 9 to 51 and plant sterol intake (mg/day) from 19 to 50. The sterol profile of IFs is highly dependent on the type and quantity of fats used in their formula. The use of bovine milk fat and milk fat globule membrane in the IFs can approximate the profile of animal sterols to those found in HM, though cholesterol intakes in breastfed infants are still higher than in formula-fed infants.

Bioactive properties of milk proteins in humans: A review.

Many studies have demonstrated that milk protein consumption has benefits in terms of promoting human health. This review assesses the intervention studies which have evaluated potential health enhancing effects in humans following the ingestion of milk proteins. The impact of milk protein ingestion has been studied to asses their satiating, hypotensive, antimicrobial, anti-inflammatory, anticancer, antioxidant and insulinotropic properties as well as their impact on morphological modifications (e.g., muscle and fat mass) in humans. Consistent health promoting effects appear to have been observed in certain instances (i.e., muscle protein synthesis, insulinotropic and hypotensive activity). However, controversial outcomes have also been reported (i.e., antimicrobial, anti-inflammatory, anticancer and antioxidant properties). Several factors including interindividual differences, the timing of protein ingestion as well as the potency of the active components may explain these differences. In addition, processing conditions have been reported, in certain instances, to affect milk protein structure and therefore modify their bioactive potential. It is thought that the health promoting properties of milk proteins are linked to the release of bioactive peptides (BAPs) during gastrointestinal digestion. There is a need for further research to develop a more in-depth understanding on the possible mechanisms involved in the observed physiological effects. In addition, more carefully controlled and appropriately powered human intervention studies are required to demonstrate the health enhancing properties of milk proteins in humans.

Effects of Industrial Heating Processes of Milk-Based Enteral Formulas on Site-Specific Protein Modifications and Their Relationship to in Vitro and in Vivo Protein Digestibility.

Heat treatments are applied to milk and dairy products to ensure their microbiological safety and shelf lives. Types of heating processes may have different effects on protein modifications, leading to different protein digestibility. In this study, milk-based liquid nutritional formulas (simulating enteral formulas) were subjected to steam injection ultra-high-temperature treatment or in-can sterilization, and the formulas were investigated by proteomic methods and in vitro and in vivo digestion assays. Proteomic analyses revealed that in-can sterilization resulted in higher signals for N(ε)-carboxymethyllysine and dephosphorylation of Ser residues in major milk proteins than in steam-injected formula, reflecting the more severe thermal process of in-can sterilization. In vitro and in vivo digestion assays indicated that steam injection improved protein digestibility, supposedly by denaturation, while the improvement seemed to be overwhelmed by formation of aggregates that showed resistance to digestion in in-can sterilized formula. Adverse effects of heat treatment on protein digestibility are more likely to be manifested in milk-based formulas than in cow's milk. Although the differences might be of limited significance in terms of amino acid bioavailability, these results emphasize the importance of protein quality of raw materials and selection of heating processes.

Effects of human milk and formula on postprandial glycaemia and insulinaemia.

BACKGROUND/OBJECTIVES: Consumption of formula in place of human milk may produce differences in postprandial glycaemia and insulinaemia that contribute to metabolic programming in the first year of life. The objective of the current study was to determine glycaemic and insulinaemic responses to human milk compared with a typical commercial formula, and then compare 11 other formulas. SUBJECTS/METHODS: On separate mornings in random order, 10 healthy breastfeeding mothers consumed 25 g available carbohydrate portions of their own milk, a formula and reference food (25 g glucose on two occasions). In the second study, 10 different healthy subjects consumed 25 g available carbohydrate portions of 11 different commercial formulas and three reference foods (25 g glucose on three occasions). Fingerpick blood samples were taken at regular intervals over 2 h, and the glycaemic index (GI) and insulin index determined according to a standardised protocol. RESULTS: There were no significant differences in postprandial glycaemia or insulinaemia after human milk vs a typical formula (P = 0.3). Both produced a low GI (mean ± s.e.m.: 38 ± 7 vs 34 ± 7, respectively) and high insulin index (87 ± 14 vs 94 ± 16). The GI and insulin indices of the other formulas ranged from 18 ± 3 to 67 ± 6 and 53 ± 9 to 209 ± 33, respectively. CONCLUSIONS: Human milk and a typical formula elicit similar postprandial glycaemic and insulinaemic responses, but there is a wide range of responses to other formulas.

Dietary Effects on Plasma Glycerophospholipids.

OBJECTIVE: Human milk provides a complex mixture of animal lipids, whereas the fat supply of most modern infant formula is based on vegetable oils. We studied the effects of breast-feeding and of feeding infant formula either without or with dairy goat lipids on the composition of infant plasma glycerophospholipids. METHODS: Healthy-term infants were randomized double blind to feeding with infant formula based on whole goats' milk (GIF, approximately 60% milk fat and 40% vegetable oils) or a control cows' milk infant formula based on vegetable oils (VIF) from 2 weeks after birth. A reference group of fully breast-fed infants was also followed. At the age 4 months, blood samples were collected and plasma glycerophospholipids were analyzed with liquid chromatography coupled to triple quadrupole mass spectrometry. RESULTS: The group of breast-fed infants showed significantly higher contents of glycerophospholipid species containing sn-2 palmitic acid [PC(16:0/16:0) and PC(18:0/16:0)] and significantly higher contents of glycerophospholipid species containing long-chain polyunsaturated fatty acids than infants in both formula groups. The GIF group demonstrated significantly higher glycerophospholipid species containing myristic acid [LPC(14:0), PC(14:0/18:1), PC(16:0/14:0)] and palmitoleic acid [LPC(16:1), PC(16:0/16:1), and PC(16:1/18:1)] than the VIF group. CONCLUSIONS: We conclude that breast-feeding induces marked differences in infant plasma glycerophospholipid profiles compared with formula feeding, whereas the studied different sources of formula fat resulted in limited effects on plasma glycerophospholipids.

The effects of probiotics and prebiotics on the fatty acid profile and conjugated linoleic acid content of fermented cow milk.

The ability of probiotic bacteria (Lactobacillus acidophilus La5 and Bifidobacterium animalis Bb12), to produce conjugated linoleic acid (CLA) in association with Streptococcus thermophilus and Lb. bulgaricus during milk fermentation has been evaluated in this study. Pasteurized cow milk and infant formula were used. Infant formula was selected for its high linoleic acid content, for being a source of CLA and for its prebiotic compounds, e.g. galacto-oligosaccharides. The microorganisms were not able to increase the CLA content of the fermented products under the given experimental conditions. No statistically significant differences (p > 0.05) occurred between the CLA content in milk and the fermented samples. The CLA contents of 10 commercial fermented milk products were determined. The highest CLA content was observed in fermented milk containing only Str. thermophilus and Lb. bulgaricus.

Oxidative stability of structured lipid-based infant formula emulsion: effect of antioxidants.

The effect of permitted antioxidants, including α-tocopherol, ß-carotene, ascorbyl palmitate, ascorbic acid, citric acid, and their combinations, on the lipid oxidation of structured lipid (SL)-based infant formula (IF) was evaluated. The 3.5% oil-in-water IF emulsion was formulated with a human milk fat analogue enriched with docosahexaenoic acid and stearidonic acid, and the antioxidants were added at 0.005% and 0.02% of the oil. The peroxide value, anisidine value, and hexanal concentration of emulsion samples were measured over a 28-day period. The results showed that whether a compound exhibited antioxidant behavior depended on its mechanism of action, polarity, concentration, and environmental conditions. The most effective antioxidant was ascorbyl palmitate at 0.005%, and a synergistic antioxidant effect was found between α-tocopherol and ß-carotene. A high correlation was observed between anisidine value and hexanal content. Our findings have important implications for the successful incorporation of SL into IF products for infant nutrition and health.

Probiotics (Lactobacillus acidophilus and Bifidobacterium infantis) prevent NEC in VLBW infants fed breast milk but not formula [corrected].

BACKGROUND: Specific probiotics prevent necrotizing enterocolitis (NEC). A mixture of lactobacilli and bifidobacteria (Infloran) was highly effective in Asian very-low-birth-weight (VLBW) infants. We analyzed the effect of Infloran on NEC, NEC severity, and the influence of enteral feedings (breast milk vs. formula) on NEC prevention in a cohort of European VLBW infants. METHODS: Infloran was implemented for routine use at our department. VLBW infants receiving probiotics were prospectively followed (2010-2012) and compared with historic controls (2008-2009). Data on NEC, neonatal morbidity, feeding tolerance, and descriptive parameters on NEC cases were analyzed. RESULTS: Infloran had no statistically significant impact on NEC (controls: 24/233 (10.3%); probiotics: 16/230 (7%); P = 0.2). However, NEC was significantly reduced in infants of the probiotics group who were fed any breast milk (20/179 (11.2%) vs. 10/183 (5.5%); P = 0.027), whereas it was ineffective in infants exclusively fed formula (4/54 (7.4%) vs. 6/44 (13.6%); P = 0.345). Occurrence of severe NEC (IIIb), time until full feeds, and gastric residuals were similar. CONCLUSION: Infloran was of lower efficacy in a European VLBW cohort and showed a reduction of NEC only in infants fed breast milk. Future studies should investigate the influence of feeding formula or breast milk on the effect of probiotics.

Preventive effects of oral probiotic on infantile colic: a prospective, randomised, blinded, controlled trial using Lactobacillus reuteri DSM 17938.

Infants were recruited in four centres in North-West Italy. 138 infants were assessed for eligibility, 113 ones underwent randomisation and 105 completed the study. Newborns aged less than 10 days of life, with gestational age between 37 and 42 weeks, birth weight from 2,500 to 4,300 g and normal physical examination were recruitable. Premature infants and infants affected by outcomes of perinatal hypoxia or necrotising enterocolitis have been excluded. Patients were randomly assigned to receive five drops containing Lactobacillus reuteri DSM 17938 (108 cfu) with 400 UI of vitamin D3 or only 400 UI of vitamin D3 daily. The primary endpoints concern the administration of pain relieving agents (cimetropium bromide at least three times per week or simethicone at least five times per week) from baseline to 12 weeks. Additional analyses were done on the percentage of infants that switched from an exclusive breastfeeding to a partial or exclusive formula feeding from baseline to 12 weeks. Data concerning the number of calls to the paediatricians and the number of visits at paediatricians' ambulatories due to infantile colic have been collected by paediatrician and analysed. Comparing the two groups, the relative risk was 0.04 (95% confidence interval (CI)=0.01-0.31) for cimetropium bromide, 0.24 (95% CI=0.14-0.41) for simethicone and 0.37 (95% CI=0.17-0.80) for the administration of infant formula, showing a protective action of L. reuteri. The treatment group showed a lower number of paediatric consultations related to episodes of infant colic than the control group (P<0.0001). L. reuteri DSM 17938 supplementation at the tested dosage could reduce parental discomfort due to infantile colic. The consumption of this probiotic is associated with a reduction of paediatric consultations for infantile colic, as well as use of pain relieving agents and of infant formula.

Prebiotics in infant formula.

The gastrointestinal microbiota of breast-fed babies differ from classic standard formula fed infants. While mother's milk is rich in prebiotic oligosaccharides and contains small amounts of probiotics, standard infant formula doesn't. Different prebiotic oligosaccharides are added to infant formula: galacto-oligosaccharides, fructo-oligosaccharide, polydextrose, and mixtures of these. There is evidence that addition of prebiotics in infant formula alters the gastrointestinal (GI) microbiota resembling that of breastfed infants. They are added to infant formula because of their presence in breast milk. Infants on these supplemented formula have a lower stool pH, a better stool consistency and frequency and a higher concentration of bifidobacteria in their intestine compared to infants on a non-supplemented standard formula. Since most studies suggest a trend for beneficial clinical effects, and since these ingredients are very safe, prebiotics bring infant formula one step closer to breastmilk, the golden standard. However, despite the fact that adverse events are rare, the evidence on prebiotics of a significant health benefit throughout the alteration of the gut microbiota is limited.

Infant formula supplemented with low protein and high carbohydrate alters the intestinal microbiota in neonatal SD rats.

BACKGROUND: Infant microbiota is influenced by numerous factors, such as delivery mode, environment, prematurity and diet (breast milk or formula) and last but not least, the diet composition. In the diet composition, protein and carbohydrate are very important for the growth of microbiota, many infant fomulas (different ratio protein/carbohydrate) can regulate the development of gut microbiota by different metabolism. The effect of low-protein, high-carbohydrate infant formula on the establishment of microbiota remains unclear, and the effect of human breast milk on the gut microbiota of the rats has also not been reported. RESULTS: In a 7 d intervention, a total of 36 neonatal SD rats (14 d old) were randomly assigned to the following groups: (1) breast-fed group (A group); (2) low-protein, high-carbohydrate infant formula-fed group (B group); (3) human breast milk-fed group (C group). After 7 days, we selected 6 rats at random from each group to study. Microbial composition in the contents of the large intestines was analysed by Miseq Sequencing. Significantly different (p<0.05) microbial colonisation patterns were observed in the large intestines of breast-fed group from low-protein, high-carbohydrate infant formula-fed and human breast milk-fed rats, but the microbiota of low-protein, high-carbohydrate infant formula-fed group and human breast milk-fed group have high similarity. At the phylum level, the absolute quantity of Bacteroidetes, Firmicutes and Proteobacteria (p<0.001) significantly differentiated in breast-fed group from low- protein, high- carbohydrate infant formula-fed and human breast milk-fed groups. Lachnospiraceae, Bacteroidaceae, Porphyromonadaceae and Prevotellaceae were the 4 top families in breast-fed group, but the top 4 families in low-protein, high- carbohydrate infant formula-fed and human breast milk-fed groups were the same, which were Bacteroidaceae, Enterobacteriaceae, Porphyromonadaceae and Lachnospiraceae. At the genus level, Bacteroides was the most abundant division, their OTUS abundance in three groups was 14.91%, 35.94%, 43.24% respectively. CONCLUSIONS: This study showed that infant formula closer resembling human milk was more different than rats' breast milk and led to a microbiota profile similar to that for human breast milk-fed neonates. The finding could support a new thinking to develop infant formulas, and provide much more details than what is known previously.

Energetic efficiency of infant formulae: a review.

Breast-fed and formula-fed infants differ in terms of nutrient intake, growth, and metabolic and endocrine responses. The energetic efficiency, i.e. the weight or length gain per 100 kcal of energy intake, of breast-fed infants is about 11% higher than the energetic efficiency of formula-fed infants. Only limited data is available on the influence of formula composition on the energetic efficiency of infant formulae. We conducted a review of controlled trials to identify the impact of the macronutrient composition of infant formulae on energetic efficiency. An electronic literature search was conducted in February 2014. Intervention trials that investigated the effect of an infant formula with a modified macronutrient composition and reported the weight, length, and nutritional intake of apparently healthy, term, fully formula-fed infants with a normal weight were included. Thirteen trials met the inclusion criteria. The results showed no effect of the total content of energy, carbohydrate, protein, or fat on energetic efficiency. In contrast, small increasing effects of higher glycemic carbohydrates on energetic efficiency were identified. Improved fat absorption via the use of palmitic acid at the sn-2 ester position of triacylglycerol increased the energetic efficiency by 11%. The quality of formula protein, specifically an increased whey-to-casein ratio, an increased α-lactalbumin content, or a higher tryptophan content increased the energetic efficiency by about 13%. We conclude that fat absorption and protein quality have the potential to modulate energetic efficiency and may contribute to the observed differences in growth and metabolism between breast-fed and formula-fed infants.