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Inductively coupled plasma emission spectroscopic determination of nine elements in infant formula: collaborative study.

Results from a collaborative study of a method for the determination of 9 elements in infant formula, using inductively coupled plasma emission spectroscopy, are reported. Six collaborators analyzed 6 infant formulas for native and spiked levels of Ca, Cu, Fe, Mg, Mn, P, K, Na, and Zn. The within-laboratory and between-laboratory coefficients of variation were generally (69 of 108 samples) below 9% for all elements determined in all samples. Most of the average recoveries of the elements from spiked samples ranged from 90 to 105%. The method has been adopted official first action for determining Ca, Cu, Fe, Mg, Mn, P, K, Na, and Zn in infant formula.

Infant Food↗

The stereospecific triacylglycerol structures and Fatty Acid profiles of human milk and infant formulas.

BACKGROUND: The stereospecific structures of the triacylglycerol molecules in human milk differ from that of cow's milk and vegetable oils, which are the fat sources used in infant formula. In human milk, palmitic acid (16:0) is predominantly esterified in the sn2 position, whereas vegetable oils or cow's milk fat contain most of their 16:0 in the outer positions of the triacylglycerol molecules. Furthermore, human milk contains long-chain polyunsaturated fatty acids, which are not present in either cow's milk or vegetable oils. METHODS: By standard lipid analysis procedures, we examined the triacylglycerol structures and fatty acid profiles of fats from 28 infant formulas or formulas for special indications available in the Danish market from 1999 to 2003. RESULTS: The total fatty acid compositions of the formulas showed a 16:0 content almost similar to human milk, whereas the content in the sn2 position was considerably lower. The content of oleic acid was found to be equal to or higher than in human milk in 21 of 28 formulas, whereas the content in the sn2 position was higher in all but one formula. Most formulas had linoleic acid levels considerably above that of human milk. Long-chain polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) were present in all preterm formulas, but only in 3 of the term formulas. CONCLUSION: We found that most of the examined infant formulas, both preterm and term as well as special formulas, had stereospecific structures and fatty acid profiles that differed considerably from that of human milk.

Arachidonic Acid↗

Modulation of the immune system by human milk and infant formula containing nucleotides.

OBJECTIVE: To determine whether human milk and nucleotides added to infant formula at levels present in human milk enhance development of the immune system during infancy. METHODS: A 12-month, controlled, randomized and blinded, multisite feeding trial was conducted on two infant formulas: iron-fortified, milk-based control formula (Control) or the same formula fortified with nucleotides (Nucleotide). The level (72 mg/L) and ratio of individual nucleotides selected were patterned after those available in human milk. A third group fed human milk exclusively for 2 months and then human milk or Similac with iron until 12 months of age also was studied. Response to immunizations was chosen to assess development of the immune system. Infants followed the immunization schedule recommended by the American Academy of Pediatrics in 1991. OUTCOME VARIABLES: Antibody responses were determined at 6, 7, and 12 months of age to Haemophilus influenzae type b polysaccharide (Hib), to diphtheria and tetanus toxoids, and to oral polio virus (OPV) immunizations. RESULTS: Of 370 full-term, healthy infants enrolled, 311 completed the study (107 Control, 101 Nucleotide, 103 human milk/Similac with iron). Intake, tolerance, and growth of infants were similar in all three groups. Compared with the Control group 1 month after the third immunization (7 months of age), the Nucleotide group had a significantly higher Hib antibody concentration (geometric mean concentrations of 7.24 vs 4.05 micrograms/mL, respectively), and a significantly higher diphtheria antibody concentration (geometric mean of 1.77 vs 1.38 U/mL). The significantly higher Hib antibody response in the Nucleotide group persisted at 12 months. The antibody responses to tetanus and OPV were not enhanced by nucleotide fortification. There also was an effect of breastfeeding on immune response. Infants who breastfed had significantly higher neutralizing antibody titers to polio virus than either formula-fed group (1:346 vs 1:169 and 1:192 in the Control and Nucleotide groups, respectively) at 6 months of age. CONCLUSION: Infant formula fortified with nucleotides enhanced H influenzae type b and diphtheria humoral antibody responses. Feeding human milk enhanced antibody responses to OPV. Dietary factors play a role in the antibody response of infants to immunization.

Bottle Feeding↗

The presence of endotoxin in powdered infant formula milk and the influence of endotoxin and Enterobacter sakazakii on bacterial translocation in the infant rat.

Lipopolysaccharide (LPS) is a heat stable endotoxin that persists during the processing of powdered infant formula milk (IFM). Upon ingestion it may increase the permeability of the neonatal intestinal epithelium and consequently bacterial translocation from the gut. To determine the level of endotoxin present in IFM, 75 samples were collected from seven countries (representing 31 brands) and analysed for endotoxin using the kinetic colorimetric Limulus amoebocyte lysate (LAL) assay. The endotoxin levels ranged from 40 to 5.5 x 10(4) endotoxin units (EU) per gram and did not correlate with the number of viable bacteria. The neonate rat model was used to address the risk of endotoxin-induced bacterial translocation from the gut. Purified Escherichia coli LPS was administered to rat pups followed by inoculation with Enterobacter sakazakii ATCC 12868. Bacteria were isolated from the mesentery, spleen, blood and cerebral spinal fluid (CSF) of endotoxin-treated rats due to enhanced gut and blood brain barrier penetration. Histological analysis of the colon showed marked distension of the mucosal and muscular layers. It is plausible that the risk of neonatal bacteraemia and endotoxemia, especially in neonates with immature innate immune systems, may be raised due to ingestion of IFM with high endotoxin levels.

Animals↗

The energy content of infant formulas.

The reported energy content of infant formulas will vary, depending upon the method used to calculate or measure the caloric value. Manufacturers' specifications regarding the energy content of milk formulas reflects the 'metabolizable' energy. i.e., the amount of energy which is digested and absorbed by the infant. However, estimates of absorptive efficiency are based primarily upon studies in young adult subjects fed mixed diets and therefore may not be generally applicable to all neonates. The actual caloric content of formulas may be determined accurately by bomb calorimetry which is not influenced by the relative metabolic efficiency of the infant who may utilize the formula. Therefore, it may be preferable to express the caloric value of milk base formulas in terms of absolute combustible energy.

Calorimetry↗

Certification of nutrients in Standard Reference Material 1846: infant formula.

In 1996, the National Institute of Standards and Technology (NIST) released Standard Reference Material 1846 (Infant Formula), which can be used as a control material for assigning values to in-house control materials and for validating analytical methods for measurement of proximates, vitamins, and minerals in infant formula and similar matrixes. The SRM was manufactured by preparing a spray-dried formula base containing fat, protein, carbohydrates, and minerals and then combining that formula base with a dry-blend vitamin premix that supplied the vitamins. The Certificate of Analysis for SRM 1846 provides assigned values for concentrations of proximates (fat, protein, etc.), vitamins, and minerals for which product labeling is required by the Infant Formula Act of 1980 and by the Nutrition Labeling and Education Act of 1990. These assigned values were based on agreement of measurements by NIST and/or collaborating laboratories. Certified values are provided for vitamins A (trans), E, C, B2, and B6 and niacin. Noncertified values are provided for solids, ash, fat, nitrogen, protein, carbohydrate, calories, vitamin D, delta-tocopherol, gamma-tocopherol, vitamin B1, vitamin B12, folic acid, pantothenic acid, biotin, choline, inositol, calcium, phosphorus, magnesium, iron, zinc, copper, sodium, potassium, and chloride. Information values are provided for iodine, manganese, selenium, and vitamin K.

Food Analysis↗

Calcium and zinc absorption from lactose-containing and lactose-free infant formulas.

BACKGROUND: Calcium absorption is enhanced by the presence of lactose, but the quantitative significance of this effect in infant formulas is uncertain. It is also not known whether lactose affects zinc absorption. OBJECTIVE: We measured the absorption of calcium and zinc from infant formulas by using a multitracer, stable-isotope technique. DESIGN: Eighteen full-term infants (aged 8-12 wk at enrollment) were fed 2 partially hydrolyzed whey-protein-based formulas ad libitum for 2 wk per formula. The carbohydrate source was lactose in one formula and glucose polymers in the other (lactose-free). Infants were studied in a blinded crossover fashion after 2 wk of adaptation to each formula. Isotope absorption studies were conducted with a 4-tracer method in which (70)Zn and (44)Ca were provided orally and (67)Zn and (46)Ca intravenously. Zinc and calcium absorption was measured from the fractional excretion of the oral and intravenous isotopes in urine. RESULTS: Fractional and total calcium absorption was significantly greater from the lactose-containing formula than from the lactose-free formula. For total calcium absorption, the mean difference between formulas was 10.3% (P = 0.002) and 60 mg/d (P = 0.006). For zinc, fractional absorption (32 +/- 11%), total absorption, and intake did not differ significantly between the 2 formulas. CONCLUSIONS: The presence of lactose in a formula based on cow-milk protein increases absorption of calcium but not of zinc. Absorption of calcium from a lactose-free infant formula is, however, adequate to meet the calcium needs of full-term infants when the formula's calcium content is similar to that of lactose-containing, cow-milk-based infant formulas.

Administration, Oral↗

Iron absorption from experimental infant formulas based on pea (Pisum sativum)-protein isolate: the effect of phytic acid and ascorbic acid.

Infant formula based on pea (Pisum sativum)-protein isolate has been suggested as an alternative to soybean formula in countries where soybean is not a native crop, or when soybean protein cannot be used due to allergic reactions or intolerances. In the present study, Fe absorption from experimental infant formulas based on pea-protein isolate was measured in healthy non-anaemic young women. The influence of phytic acid and ascorbic acid on Fe absorption was evaluated, using a stable-isotope technique based on incorporation of Fe stable-isotope labels into erythrocytes 14 d after administration. Geometric mean Fe absorption increased from 20.7 (+1 SD 41.6, -1 SD 10.3) % to 33.1 (+1 SD 58.6, -1 SD 18.7) %; (P < 0.0001; n 10) after enzymic degradation of virtually all phytic acid. Doubling the molar ratio Fe:ascorbic acid from 1:2.1 to 1:4.2 in the infant formula with native phytic acid content also increased Fe absorption significantly (P < 0.0001; n 10); geometric mean Fe absorption increased from 14.8 (+1 SD 32.1, -1 SD 6.8) % to 22.1 (+1 SD 47.2, -1 SD 10.4) %. These results confirm the inhibitory and enhancing effects of phytic acid and ascorbic acid respectively on Fe absorption, but also indicate relatively high fractional Fe absorption from the pea-protein-based formulas. After adjusting for differences in Fe status, our data indicate that Fe absorption from dephytinised pea protein might be less inhibitory than dephytinised soybean protein as measured in a previous study (Hurrell et al. 1998).

Adult↗

Rationale for the introduction of long chain polyunsaturated fatty acids and for concomitant increase in the level of vitamin E in infant formulas.

There is significant scientific agreement that human milk is the best source of nutrients for the human infant. In addition it is also agreed that the constituents of human milk and their concentrations should form the basis of infant formula compositions. The objectives of this review are two fold: to examine the data on the long chain polyunsaturated fatty acid levels (LC-PUFA) in human milk and the rationale for inclusion of these lipids in infant formulas; secondly, as a consequence of addition of highly unsaturated lipids to infant formulas, the antioxidant requirements are increased. Therefore the effect of the addition of LC-PUFA on infant vitamin E status is also examined.

Antioxidants↗

Comparative studies of manganese binding in human breast milk, bovine milk and infant formula.

The difference in ligand localization of manganese in human breast milk, cow's milk and infant formula was investigated. Extrinsic labeling technique was used and the different manganese-binding ligands were separated by gel permeation column chromatography. Manganese was found to bind to different ligands in human milk, cow's milk and infant formula. In human milk, manganese was bound by two high molecular weight proteins, the major one of 407,300 daltons and the minor one of 128,800 daltons. The 407,300-dalton protein was homogeneous with respect to molecular weight and charge and upon saturation with manganese had a metal to protein ratio of 1:1. Cow's milk had three manganese-binding species, with molecular weights of 234,000, 83,200 and less than 1000. The 234,000-dalton manganese-binding fraction was heterogeneous and contained several species with slightly different charge as revealed by DEAE-Sephacel ion-exchange chromatography. Infant formula on the other hand had no high molecular weight manganese-binding species. All the extrinsically added manganese was found in fractions with molecular weight of less than 1000.

Animals↗

Influence of tryptophan supplementation of soy-based infant formulas on protein quality and on blood and brain tryptophan and brain serotonin in the rat model.

A 2-wk feeding study with weanling rats was conducted to investigate the effects of tryptophan supplementation of soy-based infant formulas on protein quality and on the levels of blood and brain tryptophan and brain serotonin and 5-HIAA (5-hydroxyindole-3-acetic acid), a metabolite of serotonin. The powder and liquid concentrate forms of soy-based infant formulas obtained from four manufacturers were tested. The tryptophan contents of the test soy-based formulas (10.0-12.3 mg/g protein) were considerably lower compared to those of human milk (17-19 mg/g protein). The infant formulas were fed as the sole source of protein in diets containing 8% protein, 20% fat, 5% cellulose and adequate amounts of minerals and vitamins. In general, supplementation of the diets containing test formulas with graded levels of L-tryptophan (0.1 or 0.2%) had no effect on protein quality indices based on rat growth such as PER (protein efficiency ratio), NPR (net protein ratio) and relative NPR (RNPR), but resulted in significant (p < 0.05) increases in the concentrations of tryptophan in the plasma and brain, and serotonin and 5-HIAA in brain of rats. The increased concentrations of brain tryptophan and 5-hydroxyindoles (serotonin + 5-HIAA) in rats fed tryptophan-supplemented formulas compared to those fed unsupplemented formulas support the need for further research to investigate the influence of tryptophan supplementation of soy-based infant formulas on tryptophan metabolites and their potential related effects on sleep latency and neurobehavioral developments in infants.

Animals↗

[Phosphate concentration. Does reduction in infant formula feeding modify the micro-ecology of the intestine?].

The potential influence of phosphates in formulas on intestinal microflora was studied in 25 infants, aged 8 days to 12 weeks. The babies were either fed an infant formula with the usual phosphate concentration (n = 10) or an infant formula with reduced phosphate and protein concentrations (n = 7). The microbiological findings were compared with those obtained from breastfed infants (n = 8). Low-phosphate concentrations did not correlate with a predominance of bifidobacteria or suppression of putrefactive bacteria in the feces. The fecal excretion of phosphates and fat was found to be significantly lower with mother's milk compared to formulas both rich and poor in phosphate. Protein synthesis and breakdown rates, as well as the net protein gain, did not have a significant correlation with protein intake.

Bifidobacterium↗

Infant formulas: practical answers for common questions.

The pediatric health care provider is often faced with myriad decisions related to the use of infant formula. This article compares human milk to cow's milk. It addresses the composition, classification, and use of some of the most common infant formulas manufactured for use with the term infant in the outpatient setting. Common clinical situations are discussed, including the role for low-iron, goat's milk, and follow-up formulas, and formula use for the infant with diarrhea, colic, and atopic disease. The article highlights the poor quality of research and the lack of definitive answers available to the clinician when managing the infant with atopic disease. It concludes with a review of practical aspects of infant formula feeding for use in client education and management, including guidelines for formula preparation, calculating necessary formula intake, frequency, and quantity of infant feedings, and provisions of the WIC program.

Animals↗

Palm olein in infant formula: absorption of fat and minerals by normal infants.

Palm olein, a low-melting fraction of palm oil, and soy oil can be combined to obtain fat blends with proportions of palmitic and oleic acids similar to those of human milk. We compared the absorption of fat and calcium by infants fed a formula containing a blend of palm olein (53%) and soy oil (47%) (Formula PO/S) with that by infants fed a formula containing a blend of soy oil (60%) and coconut oil (40%) (Formula S/C). In a randomized crossover design, one study was performed with each formula in each of 11 normal infants ranging in age from 27 to 161 d. Six of the infants were admitted for 72-h metabolic balance studies. In the other five infants, feces (with some admixture of urine) were collected at home for 96 h by using acid-washed cloth diapers. Mean (+/- SD) absorption of fat was 90.6 +/- 1.6% of intake when Formula PO/S was fed and 95.2 +/- 1.1% of intake when Formula S/C was fed; the difference was significant (P < 0.001). The difference in excretion of fat by infants fed the two formulas was explained by the difference in excretion of palmitic acid. Absorption of calcium averaged 39.0 +/- 8.3% of intake with Formula PO/S and 48.4 +/- 10.3% with Formula S/C; the difference was significant (P < 0.01). We conclude that fat is less well absorbed from a mixture of 53% palm olein and 47% soy oil than from a mixture of 60% soy oil and 40% coconut oil, and that absorption of calcium is less from a formula containing palm olein, presumably because of the formation of insoluble calcium soaps of unabsorbed palmitic acid.

Absorption↗

Reducing parenteral requirement in children with short bowel syndrome: impact of an amino acid-based complete infant formula.

BACKGROUND: The aim of this study was to assess the impact of an amino acid-based complete infant formula on enteral feeding tolerance and parenteral nutrition requirement in children with severe short bowel syndrome. METHODS: Four children (23 months-4.75 years) with short bowel syndrome who required long-term parenteral nutrition due to persistent feeding intolerance while receiving an extensively hydrolyzed formula were assessed before and after the commencement of an amino acid-based complete infant formula for a mean follow-up period of 48 months (range 39-51 months). Assessment included clinical monitoring of feeding tolerance and nutritional status, biochemistry, stool analysis, skin-prick testing to common food antigens, esophagogastroduodenoscopy and colonoscopy or jejunoscopy with biopsies, and measurement of disaccharidase levels and intestinal permeability. RESULTS: All patients ceased parenteral nutrition within 15 months as a result of decreased stool output and resolution of vomiting. Patients had a reduction in hospitalization (mean: 198 versus 98 days/patient/year), episodes of proven (mean: 4.3 versus 3.3/patient/year) and suspected (mean: 6.5 versus 4.0/ patient/year) bacterial sepsis and central line insertions (mean: 2.5 versus 1.5/patient/year). Intestinal permeability to lactulose fell markedly (mean: 69% versus 2.7%). Disaccharidase levels increased in all three patients undergoing repeat studies. CONCLUSIONS: An amino acid-based complete infant formula improved feeding tolerance and eliminated the need for parenteral nutrition in four children with short bowel syndrome who had previously required long-term parenteral nutrition. The clinical improvement was mirrored by improvement in measurements of intestinal function.

Acidosis↗

Dialyzability of iron, zinc, and copper of different types of infant formulas marketed in Spain.

The bioavailability of trace elements in infant formulas is affected by different physiological and dietetic factors. In vitro methods based on element dialyzability have been proposed to estimate the bioavailability. Infant formulas of the same type but from different manufacturers can differ in the salt used for supplementation and in the contents of other components that can affect mineral bioavailability. The aim of our study is to estimate the dialyzability of iron, zinc, and copper of formulas marketed in Spain, in order to detect possible differences in formulas of the same type coming from different manufacturers. At the same time, the effects of the type of formula, the composition of the protein fraction, and the mineral content on the element dialyzability are also studied. Differences are found in the dialysis percentages of the elements studied in formulas of the same type but from different manufacturers. The formulas giving the highest dialysis percentages for the three considered elements are the hypoallergenic ones based on protein hydrolysates. No differences are observed in formulas having whey or casein as the main protein fraction. Significant correlations are obtained between the element contents and the dialyzability of the elements.

Copper↗

[Evaluation of a local infant formula enriched with polyunsaturated fatty acids produced in Israel].

Polyunsaturated fatty acids (PUFA) are vital for the normal development of the brain and the eye retina in infancy. Breast milk contains significant amounts of PUFA, and compensates for their low production in infancy. Only recently a few companies with worldwide product distribution have started to enrich infant formula with PUFA. We evaluated the safety and clinical efficacy of a locally made PUFA-enriched infant formula, produced for the first time in Israel. 50 normal, full term infants participated in a prospective, randomized double-blind study. Half received a regular whey-predominant infant formula (Materna Plus), and the other half a PUFA-enriched formula (Materna Premium), both produced in Israel, for 30 days. Evaluation included physical examination, growth parameters, stool analysis, daily parental questionnaires regarding infant behavior and defecation, and developmental assessment. There were no significant differences on comparing growth parameters, infant behavior, attacks of restlessness, gas severity, or stool characteristics in the 2 groups. There were no side effects or abnormal stool findings in either group, and no differences in developmental assessment at 3 months of age. We conclude that the locally-produced PUFA-enriched infant formula is safe and clinically efficient. We assume that the lack of any effect on developmental indices is due to the relatively short exposure to the PUFA-enriched diet. Nevertheless, based on the recent literature, there is no doubt that PUFA supplementation is vital in improving infant brain and eye development.

Birth Weight↗

Concentration and distribution of sialic acid in human milk and infant formulas.

BACKGROUND: In animal studies, sialic acid supplementation is associated with increases of gangliosides in the brain and improved learning ability. Only limited data are available on the sialic acid content of human milk and infant formulas. OBJECTIVE: We compared the concentrations of oligosaccharide-bound, protein-bound, and free sialic acid in milk from mothers of full-term and preterm infants and in a range of infant formulas. DESIGN: The milk from 20 and 14 mothers of full-term and preterm infants (mean gestational age: 31 +/- 3 wk), respectively, was collected at 4 stages of lactation (colostrum, transition, 1 mo, and 3 mo) and compared with 21 different infant formulas. RESULTS: Total sialic acid concentrations were highest in colostrum (x +/- SEM: 5.04 +/- 0.21 mmol/L in full term) and decreased by nearly 80% over the next 3 mo. Human milk from mothers of preterm infants contained 13-23% more sialic acid than did milk from mothers of full-term infants at 3 of the 4 lactation stages (P < 0.02). The sialic acid content of most formulas was <25% of that found in mature human milk (P < 0.01). Most of the sialic acid in the formulas ( approximately 70%) was bound to glycoproteins, whereas in human milk most sialic acid was bound to free oligosaccharides. CONCLUSIONS: Human milk, including milk from mothers of preterm infants, is a rich source of oligosaccharide-bound sialic acid, which contrasts with the relatively small amounts found in infant formulas. The nutritional significance of sialic acid is presently unknown, but it is plausible that it is a conditional nutrient that contributes to sialic acid accretion in the brain.

Adult↗