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Effects of pH variation and NaCl on in vitro digestibility of cow's milk proteins in commercially available infant formulas.

Allergenicity and antigenicity of food proteins are generally dependent on their heat-stability and resistance to digestive enzymes. Using the methods of SDS-PAGE and immunoblots, we assessed peptic-digestibility of major milk proteins (casein, beta-lactoglobulin and alpha-lactalbumin) in commercially available infant formulas in acidic pH range (pH 1.5 to 4.0), and we also investigated the effect of NaCl on peptic-digestibility of cow's milk proteins at pH 2.0. The profile of peptic-digestion of casein was similar at pH range from 1.5 to 3.5 where the intact protein of casein rapidly disappeared, whereas slow digestibility of the protein was found at pH 4.0. Beta-lactoglobulin and alpha-lactalbumin were digested at pH range from 1.5 to 2.5 and were almost entirely resistant to peptic digestion at over pH 3.0. In the presence of NaCl at pH 2.0, casein showed a good digestibility by pepsin similar to that in the absence of NaCl, in contrast to beta-lactoglobulin and alpha-lactalbumin both having their peptic-digestibility decreased in the presence of 0.2 M NaCl. As the state of the stomach in new born infants shows low amounts of secretary pepsin and out of optimum pH of peptic activity, low digestibility of beta-lactoglobulin and alpha-lactalbumin in cow's milk based infant formulas at over pH 3.0 is supposed to be responsible for their allergenicity.

Animals↗

Iron availability from an infant formula supplemented with bovine lactoferrin.

Iron balance studies were performed in 16 term infants from their 3rd until their 17th week of life. The balance studies were performed at home and comprised five periods with an interval of 3 to 4 weeks, each consisting of three 24-hour collections of milk and stool samples. Seven infants were fed an adapted infant formula supplemented with bovine lactoferrin (100 mg/100 ml) and nine received the same formula without lactoferrin. The lactoferrin supplemented group received 169 micrograms iron/kg b.w. x day and retained 63 micrograms/kg b.w. x day. The mean iron intake of infants fed with the adapted formula without supplementation of lactoferrin was 118 micrograms/kg b.w. x day. The retention of iron was 43 micrograms/kg b.w. x day. Mean percentage retention of iron in the supplemented group was 36%, in the non-supplemented group 28%.

Biological Availability↗

Determination of Cd, Cu, Pb and Zn content of infant formulas by differential pulse anodic stripping voltammetry (DPASV).

The differential pulse anodic stripping voltammetry (DPASV) method described is based on the one reported by Hasse et al., but adapted to normal laboratory conditions. The values obtained in the estimation of the analytical parameters (linearity, detection and quantification limits, precision and accuracy) show that in the conditions described the method is sensitive enough, reliable and useful for determining these elements in infant formulas. A comparison between DPASV and atomic absorption spectroscopy (AAS) methods in the conditions described here shows that the former is less sensitive but that they are similar in precision. The cadmium, copper, lead and zinc contents of different types of infant formulas marketed in Spain are reported.

Electrochemistry↗

Iodine in drinking water varies by more than 100-fold in Denmark. Importance for iodine content of infant formulas.

The iodine intake level of the population is of major importance for the occurrence of thyroid disorders in an area. The aim of the present study was to evaluate the importance of drinking water iodine content for the known regional differences in iodine intake in Denmark and for the iodine content of infant formulas. Iodine in tap water obtained from 55 different locations in Denmark varied from <1.0 to 139 microg/l. In general the iodine content was low in Jutland (median 4.1 microg/l) with higher values on Sealand (23 microg/l) and other islands. Preparation of coffee or tea did not reduce the iodine content of tap water with a high initial iodine concentration. A statistically significant correlation was found between tap water iodine content today and the urinary iodine excretion measured in 41 towns in 1967 (r=0.68, P<0.001). The correlation corresponded to a basic urinary iodine excretion in Denmark of 43 microg/24h excluding iodine in water and a daily water intake of 1.7 l. The iodine content of infant formulas prepared by addition of demineralized water varied from 37 to 138 microg/l (median 57 microg/l, n=18). Hence the final iodine content would depend heavily on the source of water used for preparation. We found that iodine in tap water was a major determinant of regional differences in iodine intake in Denmark. Changes in water supply and possibly water purification methods may influence the population iodine intake level and the occurrence of thyroid disorders.

Adult↗

Anaphylactic sensitizing power of selected infant formulas.

The purpose of the present study was to evaluate the anaphylactic sensitizing power of cow milk, soy milk, casein hydrolysate, and a new cow collagen soy protein hydrolysate (CCSPH) infant formula in a guinea pig model of anaphylactic sensitization. Various groups of animals were fed these formulas for 37 days following which they were challenged intravenously either with the sensitizing constituent or one of the infant formulations. The results of these studies indicate a high degree of sensitizing capability of cow milk formula (80% fatal and 20% nonfatal) with reactions in guinea pigs challenged with BLG and no reactions when challenged with casein hydrolysate. In animals sensitized to soy formula there were only nonfatal reactions in 30% when challenged with soy protein. Casein hydrolysate and CCSPH were shown to be nonsensitizing. The results of these studies support he use of derivative infant formulas for the prevention of cow's milk hypersensitivity in infants.

Allergens↗

Erythrocyte incorporation of iron by infants: iron bioavailability from a low-iron infant formula and an evaluation of the usefulness of correcting erythrocyte incorporation values, using a reference dose or plasma ferritin concentrations.

Bioavailability of iron (Fe) from a low-Fe infant formula was determined by erythrocyte incorporation of 58Fe 14 d after administration in ten healthy, non-Fe-deficient infants. Two feeding protocols were compared, with each infant acting as his/her own control. At 140 and 154 d of age, infants were fed 1000 g of 58Fe-labelled formula (1.44 mg total Fe/1000 g) as six feeds over 24 h (Protocol A) or as two feeds/day on three consecutive days (Protocol B). A water solution with 57Fe and ascorbic acid was given separately as a reference dose in both study protocols. Erythrocyte incorporation of 58Fe and 57Fe was determined by thermal ionisation mass spectrometry. Geometric mean 58Fe incorporation was 7.6% (range 3.3-13.5%) with Protocol A as compared to 10.6% (range 6.7-18.6%) with Protocol B (P = 0.05); paired t test. Inter-individual variability of 58Fe was not reduced by correcting for the incorporation of 57Fe from the reference dose, or by correcting for plasma ferritin concentration. Fractional erythrocyte incorporation of Fe from low-Fe infant formula was in the same range as our earlier published data on erythrocyte incorporation of Fe from human milk extrinsically labelled with 58Fe (Davidsson et al. 1994a). The methodological evaluations included in this study clearly indicate the importance of using standardised study protocols when evaluating Fe bioavailability in infants. Corrections of erythrocyte incorporation data based on plasma ferritin or erythrocyte incorporation of Fe from a reference dose were not found to be useful.

Biological Availability↗

Stability of vitamin and mineral concentrations of a low-birth-weight infant formula during continuous enteral feeding.

The stability of several vitamins and minerals of a new formula for premature infants, Similac Special Care, was examined following passage through a simulated continuous infusion apparatus designed to duplicate that used for continuous enteral feeding in infants. The concentrations of calcium, iron, zinc, copper, magnesium, vitamin A, vitamin C, and vitamin E were measured before and after infusion at rates appropriate for delivering 120 calories/kg to infants weighing 733 and 1,000 g. Following passage through this apparatus, significant reductions were noted for calcium (44-54%), iron (23-34%), and zinc (18-32%). Concentrations of copper, magnesium, and vitamins A, C, and E remained stable. When another formula commonly used for premature infants, Similac 24LBW, was subjected to similar analysis, the concentrations of all vitamins and minerals studied remained stable. Our study demonstrates that infants fed Similac Special Care by continuous infusion may not receive the quantity of calcium, iron, and zinc implied by the product label.

Calcium↗

Infant formulas: evidence of the absence of pesticide residues.

Concern about the effect of potential pesticide residues on the safety of the U.S. food supply has led to extensive modeling and projections of worst-case scenarios. Many risk assessment models project risk based on an assumption of the presence of pesticide residues at the tolerance level or at a level equivalent to the limit of analytical detectability. Often, actual residue data, and the variability of analytical detection limits, are ignored in favor of simpler models. Data presented here demonstrate the absence of detectable levels of pesticides in infant formula. The range of detection limits of analytical methodology employed also are presented. A rationale for the absence of pesticide residues in infant formulas derived from plant and animal sources is presented which obviates worst-case scenario calculations of risk based on pesticide residue tolerance levels or method detection limits.

Food Handling↗

The growth profile, thermotolerance and biofilm formation of Enterobacter sakazakii grown in infant formula milk.

AIMS: To study the growth, thermotolerance and biofilm formation of the emergent pathogen Enterobacter sakazakii in infant formula milk (IFM). METHODS AND RESULTS: The temperature range, death kinetics and biofilm formation of E. sakazakii were determined using impedance microbiology and conventional methods. In IFM the organism grew as low as 6 degrees C and optimally at 37-43 degrees C. In faecal coliform tests, 23% of strains (n = 70) produced gas from lauryl sulphate broth (LSB) at 44 degrees C after 48 h incubation. Three strains failed to grow in LSB at any of the temperatures. The D-value of cells suspended in IFM was determined between 54 and 62 degrees C. The resultant z-value was 5.7 degrees C. The organism was able to adhere and grow on latex, polycarbonate, silicon and to a lesser extent stainless steel. CONCLUSIONS: Enterobacter sakazakii was able to grow at refrigeration temperatures and on infant-feeding equipment. The thermotolerance of the organism was similar to other Enterobacteriaceae and should be killed during standard pasteurization treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Enterobacter sakazakii has been associated with infant meningitis through consumption of contaminated IFM. Enterobacter sakazakii is able to grow in IFM during storage at refrigeration temperatures and attach to infant-feeding equipment, which may become reservoirs of infection.

Animals↗

Nutrient retention in preterm infants fed standard infant formulas.

Our purpose was to compare nitrogen, mineral, and zinc balance in preterm infants fed standard infant formulas, Similac With Iron and Similac With Whey + Iron. Nitrogen and magnesium balances were similar during both feeds, and met estimated fetal requirements. Infants absorbed and retained (milligrams per kilogram per day) more calcium, phosphorus, and zinc when fed Similac With Iron. However, retention of calcium, phosphorus (both formulas), and zinc (Similac With Whey + Iron) was inadequate to meet estimated fetal requirements. These findings are important in the rapidly growing preterm infant, who is already at risk for the development of rickets and zinc deficiency and may be fed either formula on discharge from the newborn nursery.

Anthropometry↗

Effect of amino acid supplementation on protein quality of soy-based infant formulas fed to rats.

The powder forms of soy-based infant formulas obtained from four manufacturers were fed to weanling rats for two weeks, as the sole source of protein in diets containing 8% protein, 20% fat, and adequate amounts of minerals and vitamins. The relative protein efficiency ratio (RPER) and the relative net protein ratio (RNPR) values (casein + methionine = 100) of diets containing unsupplemented formulas were 71-81 and 78-85, respectively. Supplementation of the formula diets with lysine (0.2%), methionine (0.2%), threonine (0.1%) or tryptophan (0.05%) increased the level of the supplemental amino acid in rat serum but generally failed to improve the RPER or RNPR values. Addition of all four essential amino acids to the formula diets, however, caused a marked improvement in their protein quality (RPER or RNPR values = 100). The data suggested that proteins in soy-based formulas could be marginally co-limited in several indispensable amino acids.

Amino Acids↗

Upper limits of zinc, copper and manganese in infant formulas.

Upper limits are proposed for zinc, copper and manganese in infant formulas. At these limits intakes would be lower than would intakes shown to be associated with toxicity, but the upper limits of an entirely safe range of intake remain uncertain. The proposed limits provide a considerable margin beyond normal nutritional requirements, and it is not recommended that formulas should typically contain these quantities. The proposed upper limits (per 100 kcal) are 1.5 mg of zinc, 200 micrograms of copper and 50 micrograms of manganese.

Copper↗

Presence of bovine leptin in edible commercial milk and infant formula.

Leptin is a hormone secreted by the adipocytes that contribute to the control of energy balance, and circulating leptin levels reflect the amount of adipose tissue in the body, helping to regulate food intake and energy expenditure. Since it has been shown that human milk contains immunoreactive leptin, which is identical to intact human leptin, we decided to investigate the possible presence of immunoreactive bovine leptin in different kinds of common commercial milk. To determine the presence or absence of immunoreactive leptin in bovine milk for human consumption, 81 samples (66 commercial pasteurized milk and 15 artificial formulae for new-born babies) of the most common Spanish commercial types of milk were studied. All samples were evaluated before and after centrifugation, and leptin levels were measured by RIA. Leptin was detected in all samples and RIA standard curves were not perturbed when centrifuged and non-centrifuged milk replaced the buffer. Mean values of leptin in full-cream, semi-skimmed and skimmed samples, were: 5.7+/-0.3 ng/ml, 4.1+/-0.1 ng/ml, 3.7+/-0.1 ng/ml (significantly different). Leptin values were reduced after centrifugation. A significant correlation was observed between leptin levels and lipid content (p<0.0005, r=0.67) while no correlation was observed with respect to carbohydrate and protein levels. Interestingly, some preparations of infant formulae present very high leptin values reaching up to 18.9 ng/ml. In conclusion, leptin is present in significant and variable concentrations in edible commercial bovine milk, with higher concentrations in infant formula.

Animals↗

Manganese absorption from human milk, cow's milk, and infant formulas in humans.

Manganese absorption from human milk, cow's milk, and infant formulas was studied in humans by using extrinsic labeling of the diets with manganese 54 or manganese 52 and whole-body retention measurements. The fractional manganese absorption from human milk (8.2% +/- 2.9%) was significantly different when compared with cow's milk (2.4% +/- 1.7%), soy formula (0.7% +/- 0.2%), and whey-preponderant cow's milk formula with 12 mg/L of iron (1.7% +/- 1.0%) and without iron fortification (2 mg/L of iron) (3.1% +/- 2.8%), while no significant difference was observed between a whey-preponderant cow's milk formula with 7 mg/L of iron (5.9% +/- 4.8%) and human milk. The total amount of absorbed manganese was significantly higher from the non--iron-fortified cow's milk formula (2 mg/L of iron) as compared with human milk, while no significant differences were observed for the other milks and formulas.

Absorption↗

Reverse phase high pressure liquid chromatography of vitamin A in margarine, infant formula, and fortified milk.

Retinal was determined in margarine (50 mg), infant formula (1 ml), and fortified milk (1 ml) by saponification in centrifuge tubes, extraction of the unsaponifiable lipid with hexane, and high pressure liquid chromatography (HPLC) in 90% methanol on a 25 cm x 3.2 mm column containing 10 micrometer LiChrosorb reverse phase. beta-Carotene was determined using the same column and 99% methanol as eluant. The vitamins in the eluate were identified and measured from their absorption at 325 (retinol) and 453 nm (beta-carotene), using a computing integrator. Retinol and carotene were prominent peaks in the chromatograms from properly fortified samples and were satisfactorily separated from other materials. In a survey of 12 different margarines for retinol, the results from liquid chromatography agreed with those of a variety of spectrophotometric and fluorometric procedures but they were obtained with greater ease and they could be interpreted more confidently. The recovery of retinol from oil was better than 99%. The coefficients of variation was 6.8% for 12 replicate analyses of a margarine for retinol and 5.4% for 10 replicate analyses of a margarine for beta-carotene.

Animals↗

Effects of exogenous surfactant on acute lung injury induced by intratracheal instillation of infant formula or human breast milk in rabbits.

BACKGROUND: An animal experimental model of acute lung injury after intratracheal instillation of acidified milk products has been recently demonstrated. Exogenous administration of surfactant has proved to be successful treatment for acute lung injury induced by many causes including acid aspiration. The authors conducted this study to investigate whether exogenous surfactant can reduce the magnitude of lung damage induced in rabbits by acidified milk products. METHODS: The lung injury was induced by intratracheal instillation of acidified human breast milk or acidified infant formula (0.8 ml/kg, pH 1.8). Thirty minutes after the insult, some animals were treated with intratracheal surfactant 100 or 200 mg/kg. Lung compliance and alveolar-to-arterial oxygen gradient were recorded during ventilation. After 4 or 12 h, the lungs were excised to determine physiologic and histologic lung damage. Albumin, interleukin-8, and eicosanoids in bronchoalveolar lavage fluid and superoxide production by neutrophils were measured. RESULTS: The acidified milk products increased A-aD(O2)(550+/-52 and 156+/-28 mmHg; mean+/-SD at 4 h in saline solution and infant formula groups, respectively), lung wet-to-dry weight ratio (6.6+/-0.5 and 5.6 +/- 0.2), %neutrophils in bronchoalveolar lavage fluid (84+/-4% and 8+/-20%), and decreased compliance (0.76+/-0.09 and 1.90+/-0.11 ml/cm H2O). Surfactant improved these variables in a dose-dependent manner (A-aDO2 = 363+/-50 and 237+/-55 mmHg in 100-mg/kg and 200-mg/kg surfactant groups). Surfactant attenuated extensive histologic changes caused by the milk products. Superoxide production was less in rabbits receiving surfactant than in those not receiving it. CONCLUSION: Exogenous surfactant improved physiologic, histologic, and biochemical lung injury induced by acidified milk products in a dose-dependent manner. The effectiveness of surfactant may be caused, in part, by inhibition of neutrophils' sequestration and activation. These data indicate that intratracheal instillation of surfactant may be a promising therapeutic modality in acute lung injury resulting from aspiration of acidified milk products.

Animals↗

Effect of iron fortification of infant formula on trace mineral absorption.

This study was designed to examine whether iron fortification of infant formulas has an effect on utilization of other nutrients, particularly the trace elements zinc and copper. Metabolic balance studies were performed with seven normal infants who were between 43 and 420 days of age. Two formulas of nearly identical composition except for iron concentration (10.2 and 2.5 mg/L) were fed. Each infant had four balance studies performed, two while being fed formula 10.2 and two while being fed formula 2.5, in an alternating sequence. No effect of formula iron concentration was evident on absorption and/or retention of nitrogen, fat, calcium, and magnesium. Although absorption of phosphorus was significantly (p less than 0.05) less with formula 10.2 than formula 2.5, the difference was trivial. No effect on absorption of zinc was seen. However, absorption of copper was only 13.4% (SD 13.0) of intake when formula 10.2 was fed, compared with 27.5% (SD 15.3) of intake when formula 2.5 was fed. The difference was statistically significant (p less than 0.01). We conclude that iron in amounts present in iron-fortified formulas has a measurable effect on copper utilization. Because the magnitude of the effect is relatively small, we doubt that the finding is clinically relevant.

Copper↗

Enterobacter sakazakii: an emerging pathogen in powdered infant formula.

Enterobacter sakazakii represents a significant risk to the health of neonates. This bacterium is an emerging opportunistic pathogen that is associated with rare but life-threatening cases of meningitis, necrotizing enterocolitis, and sepsis in premature and full-term infants. Infants aged <28 days are considered to be most at risk. Feeding with powdered infant formula (PIF) has been epidemiologically implicated in several clinical cases. Infants should be exclusively breast-fed for the first 6 months of life, and those who are not should be provided with a suitable breast-milk substitute. PIF is not a sterile product; to reduce the risk of infection, the reconstitution of powdered formula should be undertaken by caregivers using good hygienic measures and in accordance with the product manufacturer's food safety guidelines.

Cronobacter sakazakii↗