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Supplementation of infant formula with the probiotic lactobacillus reuteri and zinc: impact on enteric infection and nutrition in infant rhesus monkeys.

UNLABELLED: Gut colonization by may have beneficial effects on infant health or capacity to resist infectious disease. Zinc supplementation has also been proposed to increase infants' resistance to disease; however, many studies have yielded conflicting results. OBJECTIVES: To study effects of probiotic supplementation of infant formula (with or without supplemental zinc) on nutritional status, gut colonization and the ability to resist gastrointestinal infection in an infant rhesus monkey model. METHODS: Infant monkeys were fed control infant formula (5 mg Zn/L), control formula with or control formula with and supplemental zinc (15 mg Zn/L) from birth to 4 months. Growth, nutritional status, mineral absorption, intestinal colonization and frequency and severity of enteropathogenic -induced gastroenteritis were monitored. RESULTS: Gastrointestinal colonization was achieved and was associated with increased ileal villous surface area and improved hematocrit, with no adverse effects on growth or nutritional indices. Fortification to 15 mg Zn/L reduced plasma copper, erythrocyte Cu/Zn-superoxide dismutase, hemoglobin, and iron absorption. Infants fed -supplemented formula had reduced diarrhea severity throughout the study period and recovered more rapidly from acute diarrhea than the other groups. CONCLUSION: -supplementation of infant formula is safe, improves iron status and decreases diarrhea severity in infant rhesus monkeys and thus may help protect formula-fed human infants from infection and nutritional deficiencies.

Animals↗

Estimation of the caries-related risk associated with infant formulas.

PURPOSE: Baby bottle tooth decay (BBTD) affects 6% of children under three years of age and is associated with inappropriate bottle use. The objective of this study was to estimate the caries-related risk associated with 26 infant formulas and whole milk. METHODS: First, the plaque pH of adult volunteers was monitored before and after an oral rinse with infant formula to determine the minimum pH obtained in response to each formula. Second, Streptococcus sobrinus 6715 was cultured in each infant formula, and the increase in the number of colony forming units was measured. Third, each infant formula was incubated with powdered enamel and the solubility of enamel mineral was calculated in the absence of bacteria. Fourth, each formula was mixed with standardized concentrations of acid to determine the buffering capabilities. Finally, enamel windows were created on extracted permanent molars and exfoliated primary incisor crowns that were then colonized with mutans streptococci and incubated with infant formula. Caries was assessed visually and radiographically for 18 weeks. The length of time required for the development of enamel caries, dentinal caries and pulpal involvement was recorded. RESULTS: One-way or two-way ANOVA of these five assays demonstrated that 1. Plaque pH varied in response to oral rinsing with infant formula and most formulas did have the ability to reduce the pH significantly below the pH obtained after rinsing with water 2. Some infant formulas supported significant bacterial growth 3. Enamel mineral was dissolved by incubation with certain infant formula 4. The buffer capacity varied among the infant formulas tested 5. The length of time required for caries to reach dentin or pulp differed for the formulas, with some formulas causing dentinal caries by 3.4 weeks and pulpal involvement by 7.2 weeks.

Acids↗

Fatty acid compositions of colostrum, cord blood, maternal blood and major infant formulas in Japan.

Lipid profiles in colostrum, cord blood, maternal blood and major infant formulas in Japan were analyzed. In the first part of the study, colostrum obtained from 36 normal delivery women and six kinds of infant formulas provided by three major milk companies were analyzed for their fatty acid composition using capillary gas-lipid chromatography. Although enriched with docosahexaenoic acid (DHA), the percent composition of DHA in the six infant formulas (0.15-0.21%) was significantly lower than that in the colostrum (1.1 +/- 0.54). Arachidonic acid (AA) and eicosapentaenoic acid (EPA) were present in the colostrum but not detectable in the infant formulas. It is recommended that although the exact amount of specific fatty acids needed in the infant diet was not completely known, to be as close as possible to natural breast milk, the level of DHA, EPA and AA should be raised in the infant formulas. In the second part of the study, 19 pairs of maternal and cord blood were analyzed for their lipid profile. All samples were from normal vaginal delivery. The measurement of cholesterol, triglycerides, phospholipids and free fatty acids was performed with commercially available enzymatic methods on an automated discrete random access analyzer. Total fatty acid was determined as described in the first part of the study. The results were analyzed with Spearman's rank correlation coefficient. No correlation could be found between maternal and fetal concentrations of cholesterol, triglycerides, phospholipids or total fatty acids. Correlation could be found in non-esterified fatty acids, in palmitic acids, and oleic acid levels. It was concluded that the lipid transport and metabolism in the fetal-placenta unit is complex and further delicate investigation is required.

Adult↗

A critical review of methods for comparing estrogenic activity of endogenous and exogenous chemicals in human milk and infant formula.

The two primary sources of nutrition for infants are human milk and infant formula. Both contain an array of endogenous and exogenous chemicals that may act through many separate hormonal mechanisms. The safety of infant nutrition sources has been questioned based on the possibility that exogenous chemicals may exert adverse effects on nursing or formula-fed infants through estrogen-mediated mechanisms. In response to these and other concerns, the National Research Council recommended assessing the estrogenic potency of natural and anthropogenic hormonally active agents. Furthermore, the Endocrine Disruptor Screening and Testing Advisory Committee of the U.S. Environmental Protection Agency specifically recommended testing chemicals present in human milk as a representative mixture to which large segments of the population are exposed. To date, no clinical or epidemiologic evidence demonstrates that levels of chemicals currently found in human milk or infant formulas cause adverse effects in infants. Nonetheless, the question is sufficiently important to warrant a consideration of how best to evaluate potential estrogenic risks. We reviewed the types of data available for measuring estrogenic potency as well as methods for estimating health risks from mixtures of chemicals in infant nutrition sources that act via estrogenic mechanisms. We conclude that the science is insufficiently developed at this time to allow a credible assessment of health risks to infants based on estimates of estrogenic potency or on an understanding of toxicologic effects mediated by estrogenic mechanisms. However, clinical and epidemiologic data for infant nutrition sources may provide insights about risks of such substances in human milk and infant formulas.

Adult↗

Upper limit of selenium in infant formulas.

At present, the amount of selenium in infant formulas is not controlled and varies depending upon the selenium content of the raw materials used in its manufacture. Since selenium deficiency has been associated with two diseases of childhood, prudence dictates that the concentration of selenium in infant formula be standardized. Extrapolation from studies with human adults indicates that a daily intake of 10 microg of selenium is sufficient to meet the nutritional requirement of the infant while providing a reasonable margin of safety. Extrapolation from adult studies also suggests that intakes of 75-160 microg/d might have harmful effects in infants. On the other hand, no cases of selenosis in infants have been reported in high selenium areas of the United States, where human breast milk supplies as much as 47 microg/d. Therefore, it is proposed that infant formulas contain enough selenium to provide 10-45 microg/d.

Female↗

Potential renal solute load of infant formulas.

The potential renal solute load (PRSL) of infant feedings is the sum of dietary nitrogen (expressed as mmol of urea, i.e., mg nitrogen divided by 28), sodium, potassium, chloride and phosphorus. The PRSL determines the renal solute load, and, therefore, the osmolar concentration of the urine. When water intake is reduced and/or water losses are increased, the renal concentrating ability may be exceeded, and negative water balance (dehydration) may ensue. Under these circumstances, feedings providing high PRSL lead more rapidly to dehydration than do feedings providing lower PRSL. On the basis of simulated clinical situations and epidemiologic data, it is concluded that conventional infant formulas (PRSL 135-177 mosmol/l, or 20-26 mosmol/100 kcal) provide a satisfactory margin of safety. A feeding providing the upper limits for concentrations of protein and electrolytes specified by the Food and Drug Administration rule does not afford a satisfactory margin of safety. It is recommended that the upper limit for protein content of infant formulas be decreased from 4.5 g/100 kcal to 3.2 g/100 kcal and that an upper limit for phosphorus concentration of infant formulas be set at 93 mg/100 kcal. Maximum PRSL will then be 221 mosmol/l (33 mosmol/100 kcal).

Electrolytes↗

Choline and choline esters in human and rat milk and in infant formulas.

Large amounts of choline are required in neonates for rapid organ growth and membrane biosynthesis. Human infants derive much of their choline from milk. In our study, mature human milk contained more phosphocholine and glycerophosphocholine than choline, phosphatidylcholine, or sphingomyelin (P < 0.01). Previous studies have not recognized that phosphocholine and glycerophosphocholine exist in human milk. Concentrations of choline compounds in mature milk of mothers giving birth to preterm or full-term infants were not significantly different. Infant formulas also contained choline and choline-containing compounds. In infant formulas derived from soy or bovine milk, unesterified choline, phosphocholine, glycerophosphocholine, phosphatidylcholine, and sphingomyelin concentrations varied greatly. All infant formulas contained significantly less phosphocholine than did human milk. Soy-derived formulas contained significantly less glycerophosphocholine (P < 0.01) and phosphocholine (P < 0.01) and more phosphatidylcholine (P < 0.01) than did human or bovine milk or bovine milk-derived infant formulas. Rat milk contained greater amounts of glycerophosphocholine (almost 75% of the total choline moiety in milk) and phosphocholine than did human milk. When dams were provided with either a control, choline-deficient, or choline-supplemented diet, milk composition reflected the choline content of the diet. Because there are competing demands for choline in neonates, it is important to ensure adequate availability through proper infant nutrition. Although the free choline moiety is adequately provided by infant formulas and bovine milk, reevaluation of the concentrations of other choline esters, in particular glycerophosphocholine and phosphocholine, may be warranted.

Adolescent↗

Liquid chromatographic determination of vitamin D in milk and infant formula.

Vitamin D2 or vitamin D3 is determined by liquid chromatography (LC) in milk and infant formula. Vitamin D is extracted from the saponified sample, passed through an amino-cyano LC cleanup column to remove major interferences, and quantitated using normal phase LC. Within-day precision is 4.5% relative standard deviation (RSD); the overall method RSD (reflecting technician-to-technician, day-to-day, and within-day variability) is 7.7%. Overspike recoveries averaged 97% for milk, 98% for milk-based infant formula, and 93% for soy-based infant formula. The performance of the method is compared with that of the official AOAC vitamin D method (rat bioassay). The method is applicable to the determination of vitamin D in milk and in the major milk- and soy-based infant formulas available in the United States. The method can quantitate (but not distinguish) either vitamin D2 or vitamin D3. The method is applicable to milk and infant formula samples containing between 100 and 1500 IU vitamin D/L. Sample throughput is between 4 and 8 replicates per day.

Animals↗

Liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in milk-based infant formula using matrix solid-phase dispersion.

A liquid chromatographic method is described for analysis of all-rac-alpha-tocopheryl acetate, tocopherols, and retinyl palmitate in milk-based infant formula. The vitamins are extracted from infant formula without saponification by matrix solid-phase dispersion and quantitated by normal-phase chromatography with fluorescence detection. Retinyl palmitate and vitamin E are quantitated isocratically with mobile phases of 0.125% (v/v) and 0.5% (v/v) isopropyl alcohol in hexane, respectively. Results were similar to the certified and non-certified ranges for all-rac-alpha-tocopheryl acetate, retinyl palmitate, and tocopherols in the infant formula standard reference material (SRM) 1846. Results also compared favorably with the label declaration on a retail infant formula. Recoveries were determined on an analyte-fortified zero control reference material for milk-based infant formula and averaged 96.8% (n = 30) for retinyl palmitate and 91.5% (n = 25) for all-rac-alpha-tocopheryl acetate. Examination of 5 concentrations for each analyte gave results that were linear (r = 0.999) over the concentration examined, with coefficients of variation ranging from 1.02 to 5.86%. The method provides a rapid, specific, and easily controlled assay for analysis of retinyl palmitate and vitamin E in fortified infant formula. Additionally, the method minimizes solvent use by using only 14 mL solvent per extraction.

Animals↗

Aluminium levels in milk and infant formulae.

Aluminium levels in infant formulae purchased in 1990 and prepared as for consumption were in the range 530 micrograms/l to 640 micrograms/l for soya-based products and 27 micrograms/l to 120 micrograms/l for cows' milk-based formulae. Mean aluminium concentrations in these soya and cows' milk-based samples were, on average, 37% and 45% lower, respectively, than those of the same brands purchased between 1985 and 1987. Levels of aluminium in breast milk were in the range 3 micrograms/l to 79 micrograms/l. In the case of retail cows' milk, values ranged from 4 micrograms/l to 33 micrograms/l whilst more variable amounts of between 5 micrograms/l and 285 micrograms/l were detected in retail soya milk.

Aluminum↗

Infant formula physical stability.

The physical nature of liquid infant formula products is characterized in terms of emulsion, suspension, and solution processes. Such mixtures inevitably undergo phase separation. A variety of physical and chemical phenomena govern the gradual changes in the appearance of these products. The consequent loss of physical elegance is primarily a question of consumer acceptance. Only in the most extreme cases do the physical characteristics deteriorate to the point that swallowing and digestion are affected. Recently, both public and regulatory attention has been focused on the physical characteristics of liquid infant formula products. Formula appearance is the product aspect most readily evaluated by the consumer. The design and manufacture of products that will have consistent appearance over extended periods is a difficult technical problem. This presentation summarizes the phenomena responsible for changes in the physical characteristics of liquid infant formula products. Product defects are discussed and methods for product evaluation are described. Representative data on the effect of storage on product physical elegance also are presented.

Dietary Carbohydrates↗

Nutrient levels in infant formulas: technical considerations.

Technical considerations in the design, production, manufacture, process, and quality control of infant formulas are presented. Many of the criteria and systems used by manufacturers to assure the safety and adequacy of infant formulas have been codified by the U.S. Food and Drug Administration. Product label claims represent the minimum levels of nutrient that must be present throughout product shelf life. The precise nutrient level in an infant formula at any given time may differ from the label claim because of the variability of nutrient amounts contributed by major ingredients, a decrease of certain nutrients due to heat or oxygen exposure during processing, changes during storage, nutrient levels added to account for bio-availability, and the variation in analytical results. Infant formula manufacturers use various processes and quality control systems to assure the presence of appropriate amounts of each required nutrient in each batch. Infant formula manufacturers support the review of existing upper limits and the establishment of new limits where there is a justifiable and adequate basis to do so. Where needed, new upper limits should be set with appropriate consideration of existing technical factors affecting product formulation and nutrient content. Control of upper limits can best be achieved within the framework of existing regulations and manufacturing systems to assure that only batches of formula with appropriate levels of nutrients are introduced into commercial distribution.

Female↗

Zinc and iron bioavailability in a powder or in-bottle-sterilized infant formula estimated by in vitro and in suckling rats.

Maillard reaction and lactose isomerization may be induced during the processing involved in the manufacture of infant formulas. The effects of dehydratation and sterilization in an infant formula on iron and zinc bioavailability were studied. A powder (PIF), previously reconstituted, and an in-bottle-sterilized liquid infant formula (LIF), from the same manufacturer, were evaluated using an in vitro method and in suckling rats. After in vitro digestion the dialyzed and non-dialyzed soluble, and insoluble fractions of iron and zinc were separated. Two-week-old rat pups were fed PIF or LIF in a drinking bottle for 7 days. Infant formula intake (I), body weight and the fecal and urinary excretions were monitored and the following parameters calculated: apparent absorption (A), retention (R), and the coefficients %A/I, %R/A and %R/I. Soluble iron (dialyzed) and zinc (non-dialyzed) were higher (p < 0.001) in LIF than PIF after in vitro digestion. Insoluble iron was similar in both infant formulas but insoluble zinc was lower (p < 0.05) in LIF than PIF. Food intake (p = 0.045) and body weight on day 4 (p < 0.05) and on day 7 (p < 0.001) were lower in LIF compared to PIF. A, R (p < 0.05 for both minerals), %A/I, and %R/I (p < 0.001 and p < 0.05 for iron and zinc, respectively) were significantly lower in rats fed LIF. Similarly, the %R/A of iron was lower (p < 0.001) in this group. Hematocrit and hemoglobin did not show significant differences. Iron and zinc levels in liver, spleen and erythrocytes were similar in both groups, but skin iron concentration was higher in LIF. Therefore, in contrast with the in vitro results, consumption of the in-bottle-sterilized formula determines lower iron and zinc bioavailability compared to the reconstituted powder infant formula.

Journal Article↗

[Benefits of a thickened infant formula with lactase activity in the management of benign digestive disorders in newborns].

This study aimed at evaluating the interest of a thickened infant formula with lactase activity by comparison with a standard infant formula in the management of benign digestive disorders in infants. Infants of both sex (N =109), ranging in age from 0 to 3 months, were included in a randomised double blind trial. Infants went to the paediatrician because of benign digestive disorders such as regurgitation, eructation or hiccup, colic, persistent crying and/or meteorism. Nine hundred and three infants were included and randomised in two parallel groups: they consumed daily either the thickened infant formula with lactase activity or a standard infant formula. There were no significant difference in the infants included in both groups. Both formula were well accepted and tolerated. Growth of the infants and compliance during the study were identical and good in the two groups. The efficiency of the formula tested was showed on digestive symptoms through: a decrease of the intensity of the digestive discomforts more important in the test than in the standard formula group; a decrease of the intensity of the gaz significantly more important in the test than in the standard formula group; significant decreases in frequency and intensity of the gaz in the test group while there were no significant diminution in the standard group; This study showed the good tolerance, acceptability and efficiency of a thickened infant formula with lactase activity on benign digestive disorders of young infants.

Dietary Supplements↗

High protein pre-term infant formula: effect on nutrient balance, metabolic status and growth.

Several lines of evidence suggest that formula with protein content of 3.0 g/100 kcal does not fully meet the protein needs of very-low-birth weight infants. Our purpose was to compare nitrogen balance, metabolic status and growth in infants fed a standard (3.0 g/100 kcal; RegPro) and high (3.6 g/100 kcal; HiPro) protein infant formula. Infants were fed both formulas, each formula for one week in balanced cross-over design. Metabolic status was monitored throughout. Nutrient balance and plasma amino acids were determined at the end of each week. Data were analysed using a linear mixed model. Eighteen infants were studied. Nine infants received the RegPro and nine received HiPro formula first. Nitrogen intake, absorption and retention were greater with the HiPro formula. None of the infants developed uremia or metabolic acidosis but retinol-binding-protein and weight gain were greater with the HiPro formula. Increased protein accretion paralleled by better weight gain without evidence of metabolic stress indicates that a formula with a protein content of 3.6 g/100 kcal better meets protein needs in these rapidly-growing infants. Further studies are needed to determine whether these short-term outcomes will be translated into long-term benefits.

Cross-Over Studies↗

Scientific rationale and benefits of nucleotide supplementation of infant formula.

The present review examines the role of dietary nucleotides in infants, and the scientific rationale and benefits of nucleotide supplementation of infant formula. The immunoprotective benefits of human milk, the biology of human milk nucleotides, and the immunological and gastrointestinal effects of dietary nucleotides in animal studies and in vitro experiments are examined. Clinical studies are reviewed, especially those examining the efficacy of nucleotide-supplemented infant formula in enhancing immunity and reducing the risk of sepsis. The presence of human milk cells, and a variety of immunoactive and trophic components of human milk, can explain the reduced incidence of sepsis in breastfed term and preterm infants. Nucleotides, believed to play an immunomodulatory role, are found in lower concentrations in infant formula. Animal studies have shown that dietary nucleotides enhance a number of immune responses and the growth, differentiation and repair of the gut. Several clinical studies have reported beneficial effects of nucleotide supplementation on gut microflora, diarrhoea and immune function, and one study has reported better catch-up growth in term infants with severe intrauterine growth retardation. More basic research studying the metabolism of nucleotides in neonates is encouraged. Additional randomized controlled trials are necessary to demonstrate the clinical benefits of nucleotide supplementation of infant formula, as it cannot be presumed that nucleotides produce the same benefits for the infant as human milk. Studies are especially necessary in high-risk neonatal situations, such as extreme prematurity, significant suboptimal nutrient intake before and after birth, and recovery from gut injury.

Diarrhea, Infantile↗

Effect of lactoferrin addition on the dialysability of iron from infant formulas.

A possible enhancing effect of lactoferrin (Lf) on iron absorption by breast-fed infants has been suggested, however the available results failed to confirm this hypothesis. Nevertheless, Lf could be useful in protecting the lipid fraction of infant formulas against oxidation. Concerning the possibility of adding Lf to infant formulas with this aim, we considered it necessary to evaluate the effect of this addition on iron dialysability, which was used as a parameter indicator of bioavailability. An in vitro dialysability method was applied to three types of infant formulas, with and without Lf added, respectively. In none of the analysed formulas did the added Lf have a negative effect on iron dialysability, and in only two of them (adapted formulas) was a statistically significant (p < 0.05) increase observed, although of low practical significance value. In conclusion, iron dialysability, used as an estimate of bioavailability, seems to be neither enhanced nor lowered by Lf addition to infant formulas.

Animals↗

Thermal inactivation of Enterobacter sakazakii in rehydrated infant formula.

The presence of low levels of Enterobacter sakazakii in dried infant formula have been linked to outbreaks of meningitis, septicemia, and necrotizing enterocolitis in neonates, particularly those who are premature or immunocompromised. In the current study, the ability of 12 strains of E. sakazakii to survive heating in rehydrated infant formula was determined at 58 degrees C with a submerged coil apparatus. The observed D58-values ranged from 30.5 to 591.9 s, with the strains appearing to fall into two distinct heat resistance phenotypes. The z-value of the most heat-resistant strain was 5.6 degrees C. When dried infant formula containing this strain was rehydrated with water preequilibrated to various temperatures, a more than 4-log reduction in E. sakazakii levels was achieved by preparing the formula with water at 70 degrees C or greater.

Colony Count, Microbial↗