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Negative effect of heat sterilization on the free amino acid concentrations in infant formula.

Infant formulas are often heat sterilized in hospitals where water contamination or nosocomial infection is a concern, but there are few studies of the effect of high heat on the nutritional value of infant formula. In particular, the effect of heat sterilization on free amino acid (FAA) concentrations is seldom discussed. In view of the importance of these nutrients for infant growth, we investigated the FAA concentrations of infant formula after heat sterilization. Powdered infant formulas were reconstituted with hot water (80 degrees C) in glass bottles and placed in an autoclave for 5 min at 105 degrees C and 5600 kg/m2 of pressure. Additional samples of formula were prepared by conventional methods to serve as controls. After autoclaving, we measured the FAA concentrations with ion exchange chromatography. The results were compared with those obtained after conventional preparation. We found a 19.5% lower amount of total protein after autoclaving compared with conventional preparation. Concentrations of total FAA were significantly lower after autoclaving (696.5 +/- 101.4 vs 899.4 +/- 152.2 micromol/l, P = 0.01). The concentrations of individual amino acids were also lower in autoclaved infant formulas, with differences ranging from -4.1 to 71.5% (mean 22.6%). Concentrations of certain amino acids were more than 30% lower, such as valine (71.5%), citrulline (61.1%), glutamine (60.6%), ethanolamine (54%), and lysine (39.2%). Both essential and nonessential amino acids were similarly affected by autoclaving, 28.17 and 27.13%, respectively, lower than in controls (P = 0.37). The concentration of ammonia was significantly higher after autoclaving (645.2 +/- 76.2 vs 393.2 +/-140.7 micromol/l, P = 0.0003). However, the urea level was significantly lower after autoclaving than after conventional preparation (1110.8 +/- 162.7 vs 1426.5 +/- 209.5 micromol/l, P = 0.0004). The accumulation of ammonia may reflect degradation of protein and amino acids. Autoclaving clearly results in decreased concentrations of FAA in infant formula. The increased concentration of ammonia after autoclaving is of concern if it leads to deleterious effects.

Amino Acids↗

Enzymic flow injection determination of free L-carnitine in infant formulae.

Infant formula samples were analysed to determine their free L-carnitine content by using flow injection (FI) with an incorporated immobilised carnitine acetyltransferase bioreactor. The methodology was based on the spectrophotometric determination through its reaction with carnitine acetyltransferase coupled with acetyl coenzyme A (acetyl-CoA) and dithiobenzoate. The merging zones technique was used to minimise acetyl CoA consumption. Linearity was observed over the concentration range 10-80 mg l-1 with L-carnitine as standard (r = 0.9998) and the rate of analysis was 50 h-1 infant formula samples. The enzymic FI method afforded a low RSD (2.2%). Comparisons were made with other methods of known accuracy. The enzymic reactors were stable for 3 months when used daily at the optimum pH.

Bioreactors↗

What is the safe protein-energy ratio for infant formulas?

Infants eat primarily to satisfy energy needs and the safe amount of protein in infant formulas (ie, the amount adequate for nearly all infants) is therefore expressed as the protein-energy ratio. We studied male infants aged 8-112 d fed milk-based formulas. One group (experimental group) was fed formulas that provided protein-energy ratios of 3.73 g/MJ (1.56 g/100 kcal) from 8 to 27 d of age, gradually decreasing to 2.99 g/MJ (1.25 g/100 kcal) from 84 to 111 d of age. Growth rates and serum albumin and urea nitrogen of these infants were compared with those of a concurrently studied control group and a previously studied large reference group. Gains in weight and concentrations of serum albumin of the three groups were not significantly different. Gains in length were significantly less for the experimental group than for the reference group. Serum urea nitrogen was significantly less in the experimental group than in the control group or reference group. We conclude that the protein-energy ratios of the experimental formula diet were below the safe level. Because the decrease in growth rate of the experimental group was rather small (demonstrable only in comparison with the large reference group), and because serum albumin of the experimental group increased with age as in normally nourished infants, we suspect that the safe protein-energy ratio of infant formulas lies closer to the ratios fed to the experimental group than to the ratio [approximately 5.0 g/MJ (2.1 g/100 kcal)] in currently marketed milk-based formulas.

Blood Urea Nitrogen↗

The infant formula industry, the Infant Formula Act of 1980, and quality control.

Throughout the months following the discovery of the low-chloride problem in infant formula, the industry undertook independent and voluntary measures to ensure the compositional quality of formulas. Members of the Infant Formula Council reviewed industry procedures, practices, and policies, and submitted a detailed description of its quality control and clinical testing procedures to the Food and Drug Administration. New product concepts and product reformulation proposals are based on medical and nutritional findings, on changes in medical concepts for nutritional support, on availability of improved nutrient sources, or on improved ingredients or processing technologies. Quality control is maintained throughout the manufacturing process through inspection of raw materials, analysis of major and minor constituents, equipment and process controls, and continuous product monitoring. However, despite cooperation of the infant formula industry with FDA and Congress during the development of the infant formula bills, the proposed document was too rigid and did not take into account that manufacturing methods of a given manufacturer often vary for the same product, for different products, and on different production equipment. The statistical criteria established uneven and inconsistent requirements for various manufacturers. Congress did not forsee that the proposed regulatory procedures would significantly affect industry.

Humans↗

Colic in breast-milk-fed infants: treatment by temporary substitution of neocate infant formula.

Infant colic is a common problem characterized by excessive crying and fussing. We examined whether colic symptoms of exclusively breast-milk-fed infants would be improved by temporary substitution of Neocate, an amino acid-based infant formula, for breast milk. Six infants with colic were studied using Barr-type infant behavior diaries for a 3-5 d baseline period while they continued exclusive breast-milk-feeding, followed by a 4-8 d intervention period of exclusive Neocate feeding. All infants showed improvement in distressed behavior during intervention; five of the six improved within 1-2 d. For the period after 1 d of Neocate feeding, the total recorded crying and fussing time was reduced by an average of 42%, representing a decrease of 1.0 to 3.1 h daily. A significant difference was found between cry and fuss time at baseline versus during exclusive Neocate use. Concurrent with Neocate intervention, mothers strictly avoided all milk and dairy products. After colic symptoms improved, infants were reintroduced to breast milk, which was reasonably well tolerated in four of the six infants. Two infants had rapid recurrences of crying and fussing upon return to breastfeeding and required an additional period of Neocate feedings before subsequent reintroduction to breastfeeding. All infants exhibited colic symptoms when directly or indirectly challenged with bovine IgG (BGG), suggesting that BGG may play an etiologic role in colic. We propose that a brief intervention with Neocate, coupled with strict maternal avoidance of milk and dairy products under direct supervision of a lactation consultant, may be an effective treatment for colic in some breast-milk-fed infants.

Animals↗

Whey protein hydrolysate formula for infants with gastrointestinal intolerance to cow milk and soy protein in infant formulas.

Twenty-one infants less than 6 months of age with gastrointestinal symptoms of cow milk and/or soy protein-based infant formula intolerance (diarrhea in 14, hematochezia in 16, emesis in 8, failure to thrive in 4, and colic in 10) were treated clinically with a whey protein hydrolysate formula. Six patients improved when placed directly on the formula, and 15 remained asymptomatic or improved when given the whey hydrolysate formula following initial treatment with a casein hydrolysate or elemental formula. Eighteen had supporting evidence of an allergic basis for their symptoms, including a family history of allergies in 6, a clinical challenge with the offending formula in 1, laboratory tests consistent with atopy in 11, and/or rectal biopsy with histologic allergic features in 7. The whey hydrolysate formula may be an acceptable alternative to soy or casein hydrolysate formulas in most infants with gastrointestinal symptoms of cow milk and/or formula intolerance.

Food Hypersensitivity↗

Iron, zinc, copper and selenium status of breast-fed infants and infants fed trace element fortified milk-based infant formula.

Infants were fed cow's milk-based formulas containing 4 mg of iron/l from 1.5 to 6 months of age and their hematological status was compared to infants receiving the same formula but with 7 mg of iron/l and with breast-fed infants. One formula with 4 mg of iron/l contained iron as ferrous sulfate, in another, part of the iron was provided as bovine lactoferrin. We also studied the effect of selenium (10 micrograms/l) and copper (0.4 mg/l) supplementation on selenium and copper status. There were no significant differences in hematological indices among the groups at 6 months of age; all infants had satisfactory iron status. Serum transferrin receptor levels, a potential novel indicator of iron status, were highest in breast-fed infants, suggesting a cellular need for iron, and lowest in infants receiving formula with 7 mg of iron/l. Selenium status, as assessed by serum glutathione peroxidase activity, was similar at 6 months of age in breast-fed infants and infants fed formula fortified with selenium but lower in infants fed unfortified formula. The lowest levels of glutathione peroxidase activity were found in infants fed the highest concentration of iron (7 mg/l). Serum copper concentrations were similar in all groups, but the lowest levels were found in infants fed the highest concentration of iron. These results suggest that 4 mg of iron/l is adequate for infants up to 6 months of age and that higher levels may have some negative effects.

Blood Urea Nitrogen↗

Acidogenic potential of Soya infant formula in comparison with regular infant formula and bovine milk: a plaque pH study.

Soya infant formulas are essential for infants intolerant to cow's milk. Soya formulas contains glucose syrup or maltodextrins instead of Lactose, which has led to concern that they are potentially more cariogenic than standard infant formulas containing lactose. The study was conducted to compare the acidogenic effect of Soya Infant formula, infant formula and bovine milk. The study group consisted of 75 children in the age group of 7-10 years. The plaque pH was measured using plaque pH meter, before and after rinsing with different samples for sixty minutes Soya infant formula is found to be more acidogenic than infant formula (with lactose) and bovine milk. This study demonstrates high caries inducing potential of Soya infant formula. Further awareness of the possible role of Soya infant formula in early childhood caries is required.

Analysis of Variance↗

Methods of analysis for infant formula: Food and Drug Administration and Infant Formula Council Collaborative Study.

Because the U.S. Infant Formula Act of 1980 requires manufacturers to produce formula containing a specific minimum amount of nutrients, it became necessary to establish analytical methods for the nutrients listed in the Act. The Food and Drug Administration, the Infant Formula Council, its member companies, contract laboratories, and other government laboratories undertook a collaborative study of available methods; the specific nutrients studied to date include vitamins A, B6, C, riboflavin, and niacin, and the elements calcium, magnesium, iron, zinc, copper, manganese, sodium, and potassium. The coefficients of variation in most cases have been as good as those that could be predicted from other collaborative studies. The methods studied for these nutrients have been adopted official first action except the method for vitamin A.

Animals↗

Methods of analysis for infant formula: Food and Drug Administration and Infant Formula Council Collaborative Study, Phase III.

Phase III of the collaborative study of methods of assay for nutrients in infant formulas was conducted. The study included assay of chloride, phosphorus, proximates (ash, fat, protein, total solids, and carbohydrates), thiamine, total pantothenates, and vitamins A, B12, and E. Most of the methods were those in Official Methods of Analysis, 13th edition, with slight modifications, or methods of the Infant Formula Council. On the basis of the results obtained by the collaborators, the methods for chloride, phosphorus, proximates, thiamine, and vitamin B12 have been adopted official first action. Methods for total pantothenates, vitamin A, and vitamin E were not recommended for adoption at this time because of anticipated improvements in methodology in the foreseeable future.

Food, Formulated↗

Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis.

OBJECTIVES: To compare the effect of donor breast milk with infant formula in preterm infants. Separate comparisons with formula were made for donor breast milk that was: (1) given as a sole diet; (2) given as a supplement to mother's own breast milk; and (3) fortified with macronutrients and micronutrients. The main outcomes were death, necrotising enterocolitis (NEC), infection, growth and development. DATA SOURCES: Electronic databases-Cochrane, CENTRAL, MEDLINE, EMBASE, CINAHL, and HMIC: DH. REVIEW METHODS: Systematic review and meta-analysis of trials and observational studies of preterm or low birthweight infants. RESULTS: Seven studies (including five randomised controlled trials), all from the 1970s and 1980s, fulfilled the inclusion criteria. All studies compared the effect of sole donor breast milk with formula (combined n = 471). One of these also compared the effect of donor breast milk with formula given as a supplement to mother's own milk (n = 343). No studies examined fortified donor breast milk. A meta-analysis based on three studies found a lower risk of NEC in infants receiving donor breast milk compared with formula (combined RR 0.21, 95% CI 0.06 to 0.76). Donor breast milk was associated with slower growth in the early postnatal period, but its long-term effect is unclear. CONCLUSION: Donor breast milk is associated with a lower risk of NEC and slower growth in the early postnatal period, but the quality of the evidence is limited. Further research is needed to confirm these findings and measure the effect of fortified or supplemented donor breast milk.

Child↗

Perspectives on adverse effects of milks and infant formulas used in infant feeding.

Potential adverse effects of infant formulas and breast milk upon growth are discussed. The author's description of failure to thrive in infants receiving a chloride-deficient formula emphasizes that growth can be affected by the deficiency of nutrients such as chloride. Quality control of the manufacture of infant formulas must be monitored to ensure their safety, since they are used as the sole source of infant nutrition. As the incidence of breast feeding increases, its potential hazards must also be recognized by those who monitor the growth of infants.

Avitaminosis↗

Enterobacter sakazakii bacteriophages can prevent bacterial growth in reconstituted infant formula.

Reconstituted infant formula has been implicated in outbreaks of Enterobacter sakazakii infections, causing high mortality and serious sequelae. Current prevention methods appear to be insufficient to ensure that such foods are free of E. sakazakii. In this study, the usefulness of bacteriophages for biocontrol of E. sakazakii was investigated. Of a total of six new E. sakazakii phages isolated from sewage and UV irradiated cultures, two were selected for further study by electron microscopy, DNA restriction analysis and SDS-PAGE of structural proteins. Purified phages were used to control bacterial growth in broth medium and reconstituted infant formula. Both phages effectively prevented development of E. sakazakii in formula at various temperatures (12, 24 and 37 degrees C), the efficiency of which was dependent upon intrinsic lysis properties and the applied phage concentration. We conclude that application of specific bacteriophages may provide a means for efficient prevention of E. sakazakii infection through reconstituted infant formula.

Bacteria↗

Feeding with premature or infant formula in premature infants after discharge: comparison of growth and nutrition status.

We designed this prospective randomized controlled study to evaluate the effects of premature and standard term formula on growth, nutrient intake and biochemical response in premature infants from hospital discharge to 6 months of corrected age. Premature infants with a gestational age of < or =35 weeks and a birth weight < or =1850 gm were assigned to receive premature infant formula (n = 19) or a standard term infant formula (n = 15). No differences were found between the two groups in weight, length, or head circumference at baseline or on follow-up. Infants fed premature formula had higher blood urea nitrogen and phosphorus at 3 months of corrected age. Those on the premature formula also had higher energy intake at 1 month of corrected age. We suggest that premature infants, especially very low birth weight infants, fed preterm infant formula after discharge until 6 months of corrected age tolerate the formula well and may benefit over those standard term formula.

Female↗

Nutritional adequacy and safety of infant formulas.

The Infant Formula Act contains specific requirements for minimum and, in some cases, maximum levels for a list of nutrients that may be revised as warranted by the development of new scientific information. Formulas are required to be manufactured in accordance with quality control procedures to ensure that the safety and nutritional potency of a formula is built into the manufacturing process. A formula that does not provide the minimum level for any required nutrient shall be deemed to be adulterated and may be subject to removal from the market. A manufacturer is required to promptly notify the Secretary of the Department of Health and Human Services of instances whereby a formula does not meet the nutrient requirements, is otherwise adulterated or misbranded, and, as such, presents a risk to human health. There are other provisions in the Act, but these establish that, for infant formulas, nutritional safety is clearly recognized as an integral part of food safety.

Consumer Product Safety↗

Concentrations of Nepsilon-carboxymethyllysine in human breast milk, infant formulas, and urine of infants.

Maillard products, such as Nepsilon-carboxymethyllysine (CML), are readily formed during the manufacturing of infant formulas. Little has been known, however, about the presence of CML in human breast milk and about the uptake of CML by infants. In this study, CML was measured in the serum and breast milk of 32 healthy mothers by ELISA. CML concentrations in breast milk (137 +/- 82.7 ng/mL) were significantly lower than in the serum (399 +/- 67.8 ng/mL, p < 0.001) and on average 35-fold lower than in infant formulas (4754 +/- 4299.5 ng/mL). CML was also measured in the urine of 21 infants, which were fed with breast milk or formulas. Although there was a tendency toward higher urinary CML excretion in infants fed with hypoallergenic formulas compared to breast-fed ones, the differences were not significant. Neonates that were delivered by vaginal birth had significantly higher concentrations of CML compared to those delivered by caesarean section (1306 +/- 653 vs 601 +/- 220 ng/mL, p = 0.012). It is concluded that CML passes from the serum into the breast milk, but the levels are by far lower than in infant formulas. In very young neonates (< or =3 days), the mode of delivery has a greater influence on urinary CML excretion than the nutrition.

Breast Feeding↗

Controversies in the composition of infant formulas.

Available infant formulas contain a vast assortment of carbohydrate, protein, and fat sources in an effort to emulate the composition of human milk. Although infants receiving commercial formulas thrive, physicians should be cognizant of differences in formula composition and the research that has resulted in the differences. Such awareness permits rational and scientific recommendations both in prescription of formulas and in direction of research on the optimal formula composition for infants.

Dietary Carbohydrates↗