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A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants.

The effects of dietary docosahexaenoic acid (DHA) supply during infancy on later cognitive development of healthy term infants were evaluated in a randomized clinical trial of infant formula milk supplemented with 0.35% DHA or with 0.36% DHA and 0.72% arachidonic acid (AA), or control formula which provided no DHA or AA. Fifty-six 18-month-old children (26 male, 30 female) who were enrolled in the trial within the first 5 days of life and fed the assigned diet to 17 weeks of age were tested using the Bayley Scales of Infant Development, 2nd edition (BSID-II) (Bayley 1993) at the Retina Foundation of the Southwest, Dallas, TX. These children had also been assessed at 4 months and 12 months of age for blood fatty-acid composition, sweep visual evoked potential (VEP) acuity, and forced-choice preferential looking (FPL) acuity (Birch et al. 1998). Supplementation of infant formula with DHA+AA was associated with a mean increase of 7 points on the Mental Development Index (MDI) of the BSID-II. Both the cognitive and motor subscales of the MDI showed a significant developmental age advantage for DHA- and DHA+AA-supplemented groups over the control group. While a similar trend was found for the language subscale, it did not reach statistical significance. Neither the Psychomotor Development Index nor the Behavior Rating Scale of the BSID-II showed significant differences among diet groups, consistent with a specific advantage of DHA supplementation on mental development. Significant correlations between plasma and RBC-DHA at 4 months of age but not at 12 months of age and MDI at 18 months of age suggest that early dietary supply of DHA was a major dietary determinant of improved performance on the MDI.

Analysis of Variance↗

Cow milk allergy in infancy and hypoallergenic formulas.

Substitute feedings have been used to treat infants with cow milk protein allergy for most of this century. For the past 50 years, several infant formulas based on animal proteins, both intact and chemically modified, or on vegetable protein have been labeled "hypoallergenic." Because of the risk of anaphylaxis and other serious adverse reactions, formulas that are claimed to be hypoallergenic should be subjected to rigorous preclinical and clinical testing. At a minimum, such formulas should not provoke any allergic signs or symptoms in 90% of infants with documented cow milk protein allergy when tested in double-blind, placebo-controlled trials. A standardized definition of "hypoallergenic" will allow clinicians and parents to understand the true risks to a cow milk-allergic infant fed such hypoallergenic formulas.

Animals↗

Infant feeding: formula, solids.

This article discusses and evaluates current formulas, traces their continual improvement (based largely on new information on breast milk composition), and then discusses the question of supplemental feedings.

Adult↗

Multi-analyte optimisation of uncertainty in infant food analysis.

The Optimised Uncertainty (OU) methodology has been developed to optimise multi-analyte situations. It has then been applied to a retail survey of infant food for trace elements, classifying the food as compliant or non-compliant with the regulatory thresholds or specification limits that are appropriate for each element. The large-scale survey of infant foods was successfully adapted to allow the estimation of uncertainties, from both primary sampling and chemical analysis, for elemental concentrations in infant formula (milk) and wet meals. The analytes included in this investigation comprised both contaminants (Pb and Cd) and elements essential for child development (Zn and Cu). Optimisation of the measurement process for a 'single analyte' demonstrated the potential financial benefits of optimising future surveys for a false compliance scenario. Uncertainty estimates for the measurement of elemental concentrations in infant formula were dominated by uncertainty from the analytical method. Large potential savings (up to pounds 575,000 per batch) are predicted for both Pb and Zn by increasing the expenditure on chemical analysis to the optimal level. In comparison the uncertainty estimates for elemental concentration in wet meals showed a dominance of sampling as a source of uncertainty for Cd and Cu due to the increased heterogeneity. The feasibility of 'multi-analyte' optimisation is demonstrated for the case study of infant milk. Single analyte optimisation of the four analytes for a false compliance scenario indicated a decrease in expectations of financial loss of between 99% and 8%. An overall decrease in the total expectation of financial loss of 99% is indicated following multi-analyte optimisation.

Child, Preschool↗

A better guideline on milk requirements for babies below 6 months.

The volume of infant formula required for babies below the age of 6 months continues to pose problems both for parents and child health care workers. To investigate this, about 150 bottle-fed babies were studied every 2 months from birth for their milk intake and weight gain. They were fed on demand with full strength infant formula and weaning was started at about 4 months. Weight gain was normal, with growth patterns comparable to Cambridge babies. The mean (s.d.) daily milk volumes in millilitres consumed were: 582 (144), 847 (163), 851 (176), 812 (219) at 7 days, 2, 4 and 6 months, respectively. With such a wide range of milk intake at each age, it would be inappropriate and misleading to provide a single mean recommended volume. Thus, percentile values are suggested as a better guideline for recommended intake. Estimation was made for the volume of milk required if milk was the sole source of energy for the first 6 months.

Adolescent↗

Epidemiologic typing of Enterobacter sakazakii in two neonatal nosocomial outbreaks.

Two unrelated hospital outbreaks of Enterobacter sakazakii, involving meningitis, bacteremia, and colonization of neonates, were investigated. In each of these outbreaks, E. sakazakii was isolated from both patients and dried infant formula. In previous outbreaks, the source and mode of transmission of E. sakazakii in neonatal infections was not determined. In this study, we used a combination of typing methods (plasmid analysis, antibiograms, chromosomal restriction endonuclease analysis, ribotyping, and multilocus enzyme electrophoresis) to evaluate the isolates from each outbreak as to their relatedness. The typing results differed among outbreaks, but in each one, patient and formula isolates shared the same typing pattern. The only exceptions were disk antibiograms, which often varied among colonies selected from each of the isolates. Plasmid analysis, chromosomal restriction endonuclease analysis, ribotyping, and multilocus enzyme electrophoresis all were effective as epidemiological typing methods for E. sakazakii, especially when used in combination. By using this typing scheme, we have confirmed that E. sakazakii from intrinsically contaminated dried infant formula was the source of neonatal infection.

Anti-Bacterial Agents↗

Lead and mercury in breast milk.

OBJECTIVE: Heavy metals are potentially toxic substances, especially for the susceptible infant. Exposure to mercury (Hg) and lead (Pb) may result in neurotoxic and nephrotoxic impairment and in anemia. Previous data on breast milk Pb and Hg contents are sparse or missing for the Austrian population. No evaluations of the influence of mothers' lifestyles on Pb and Hg levels in breast milk are available. METHODS: Five- to 10-mL individual samples of breast milk were provided from healthy mothers in Vienna (urban; n = 59), Linz (industrial; n = 47), and Tulln (rural; n = 59). A questionnaire about area of residence, maternal nutrition, smoking habits, and dental fillings was filled out by the lactating mothers. Milk samples and infant formulas were lyophilized, wet-ashed with nitric acid (65%), and analyzed with atomic absorption spectrophotometry. Spiked skim milk powder was used as reference material. Statistical analysis included the Kruskal-Wallis test and multiple robust regression analysis. RESULTS: Breast milk showed low Hg and Pb concentrations (Hg: 1.59 +/- 1.21 1g/l, n = 116; Pb: 1.63 +/- 1.66 6g/l, n = 138). Eight percent of the breast milk samples marginally exceeded the screening level of 3.5 micro g/L for Hg. Austrian Pb values declined strongly during the last 20 years. Bivariate comparison revealed that the factors significantly related to metal levels in breast milk were area of residence (Hg, Pb), prematurity (Hg), consumption of fish (Pb) and cereals (Hg), vitamin supplementation (Hg), and smoking (Pb). The Hg and Pb contents of cow milk and infant formulas were far below respective guideline values. CONCLUSIONS: Neither Hg nor Pb concentrations exceeded critical levels. There are no reports on infants harmed by the intake of milk from unexposed mothers. We conclude that even theoretical risks from current Hg or Pb levels for the breastfed infant of a healthy mother can be ruled out.

Animals↗

Oral rotavirus vaccination in breast- and bottle-fed infants aged 6 to 12 months.

Oral bovine rotavirus vaccine RIT 4237 was tested at two dose levels in 217 children between 6 and 12 months of age who received either breast milk or bottle milk (cow's milk or infant formula) before vaccination. Of the children 65% were initially seronegative for rotavirus ELISA IgG and IgM antibody. The full vaccine dose (10(8.3) 50% tissue culture infective doses, TCID50) induced seroconversion rates 81% and 86% and booster response rates 69% and 64% in breast and bottle-fed children, respectively. There was no difference in the vaccine response of infants receiving cow's milk or infant formula either. It is concluded that the RIT 4237 rotavirus vaccine at the dose level 10(8.3) TCID50 gives a satisfactory response in both breast- and bottle-fed children in this age group, but multiple vaccinations may be needed for maximal efficacy.

Administration, Oral↗

The effect of diet on feces and jaundice during the first 3 weeks of life.

This study examined the relationship between fecal output and neonatal jaundice in infants exclusively fed either human milk or one of three infant formulas (whey predominant, Enfamil; casein predominant, 3305H; and casein hydrolysate, Nutramigen; all from Mead Johnson, Evansville, IN). Stool output was quantitated during the first 3 weeks of life. Jaundice was assessed by measuring serum bilirubin level and transcutaneous jaundice index. In general, after the fourth day, breast-fed infants produced lower-weight individual wet and dry stools than formula-fed infants. Cumulative wet and dry stool output was also lowest in the breast-fed infants during this time. After the first week, breast-fed infants had a higher stooling frequency than formula-fed infants. The jaundice indexes of the four groups differed significantly on all days after day 3, with highest levels in breast-fed infants and lowest levels, for unknown reasons, in those fed casein hydrolysate. The jaundice index of those fed casein hydrolysate was significantly lower than that of the other formula-fed infants on days 10-18. In the breast-fed group the decrease from day 3 to day 21 in both serum bilirubin level and the jaundice index was positively correlated with both the 21-day total wet and total dry cumulative stool weights. It is concluded that the quantity of stool excreted is related to decreases in serum bilirubin levels in infants fed human milk.

Bilirubin↗

Effects of dietary long-chain polyunsaturated fatty acids on plasma amino acids and indices of protein metabolism in infants: results from a randomized clinical trial.

BACKGROUND/AIM: Previous studies in vitro and in animals in vivo found that alpha-linolenic acid (C18:3omega3) may enhance oxidative damage of essential amino acids. We investigated whether the addition of the long-chain polyunsaturated fatty acids (LCPUFA) arachidonate (C20:4omega-6; AA) and docosahexaenoate (C22:6-omega3; DHA) in the form of egg phospholipids to infant formula affects plasma amino acid concentrations and indices of protein metabolism in term infants. METHODS: In a double-blind, randomized clinical trial, healthy infants were fed from day 5 of life formula with or without preformed LCPUFA (n = 10 and 12, respectively). At the age of 5 days and 1, 2, 3 and 4 months, blood samples were obtained and analyzed for plasma amino acids by high-performance liquid chromatography and for plasma phospholipid fatty acid composition by gas chromatography. RESULTS: At the age of 3 months, plasma threonine concentrations were significantly lower in infants receiving dietary LCPUFA than in controls (124 +/- 16 vs. 216 +/- 28 micromol/l, p < 0.05). Values of other plasma essential amino acids, total protein, albumin, creatinine and urea nitrogen did not differ between the two feeding groups throughout the study. At the age of 5 days, plasma phospholipid AA and DHA concentrations were inversely correlated with histidine concentrations (AA: r = -0.60, p = 0.01; DHA: r = -0.53, p < 0.05). At the age of 3 months, DHA concentrations were inversely related to plasma histidine, methionine and threonine concentrations (r = -0.66, -0.62, and -0.64, respectively, p < 0.05). CONCLUSIONS: The dietary LCPUFA supplementation of infant formula used in this study has no adverse effects on infant plasma amino acid concentrations and indicators of protein metabolism. Nonetheless, the apparent interaction of LCPUFA with some amino acids in formula-fed infants warrants further investigation.

Amino Acids↗

Filling the AOAC triangle with food-matrix standard reference materials.

Well-characterized reference materials are needed by laboratories in the food testing and nutrition communities to facilitate compliance with nutritional labeling laws, to provide traceability for food exports needed for acceptance in many foreign markets, and to improve the accuracy of nutrition information that is provided to assist consumers in making sound dietary choices. As a result of the enactment of the Nutrition Labeling and Education Act of 1990 and the Infant Formula Act of 1980, the National Institute of Standards and Technology (NIST) has developed a suite of food-matrix Standard Reference Materials (SRMs) characterized for nutrient concentrations. These include SRM 1544 Fatty Acids and Cholesterol in a Frozen Diet Composite, SRM 1546 Meat Homogenate, SRM 1548a Typical Diet, SRM 1566b Oyster Tissue, SRM 1846 Infant Formula, SRM 1946 Lake Superior Fish Tissue, SRM 2383 Baby Food Composite, SRM 2384 Baking Chocolate, SRM 2385 Spinach, and SRM 2387 Peanut Butter. Many of these materials were developed at the request of the food industry to populate a nine-sectored fat-protein-carbohydrate triangle developed by AOAC International. With the completion of SRM 2387, SRMs representing each sector of the triangle are now available. These food-matrix reference materials are intended primarily for validation of analytical methods for the measurement of proximates, fatty acids, vitamins, minerals, and so on in foods of similar composition. They may also be used as "primary control materials" in the value-assignment of in-house, secondary, control materials to confirm accuracy as well as to establish traceability to NIST.

Food Analysis↗

Parathyroid hormone-related peptide in lactation and in umbilical cord blood.

Parathyroid hormone-related peptide (PTHrP) is expressed in lactating rat mammary glands after suckling, as a result of increases in prolactin rather than suckling per se. In addition, PTHrP produced in the fetal parathyroid glands and placenta may be responsible for stimulation of placental calcium transport. In the current study, we used a radioimmunoassay for human PTHrP to measure levels of the peptide in (1) human breast milk, cow's milk, and two infant formulas; (2) sequential plasma samples in prepartum and postpartum lactating women; (3) women with pathologic hyperprolactinemia; and (4) human umbilical cord blood. In normal subjects, plasma PTHrP levels ranged from less than 2 to 5 pmol/liter. In contrast, human breast milk contained substantially increased levels of immunoreactive PTHrP. Similar elevations were found in cow's milk and in one infant formula. Column chromatography of breast milk demonstrated that PTHrP immunoreactivity included a region of adenylate cyclase stimulating activity, consistent with the presence of biologically active PTHrP. Plasma prepartum PTHrP values did not differ from corresponding postpartum values in lactating women. Women with hyperprolactinemia had a mean plasma PTHrP value in the high-normal range. Umbilical cord blood had considerably suppressed parathyroid hormone values but PTHrP levels that were indistinguishable from those in normal human plasma. Thus, PTHrP is present in high concentrations in breast milk but apparently does not gain access to the maternal circulation in significant amounts. In addition, women with pathologic hyperprolactinemia seem not to have increased levels of circulating PTHrP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biological effects and safety issues related to long-chain polyunsaturated fatty acids in infants.

The purpose of this workshop at the American Oil Chemists' Society Symposium, "PUFA in Infant Nutrition: Consensus and Controversies," was to enumerate the safety issues raised by the prospect of supplementing infant formulas with long-chain polyunsaturated fatty acids (LC-PUFA), to evaluate the evidence that these concerns are problematical, or theoretically problematical, and to identify the safety issues most in need of resolution. This was approached by reviewing briefly the known biological effects of LC-PUFA and how these effects might give rise to concerns about safety of LC-PUFA as components of infant formulas. Some of these issues were then discussed in more detail by invited participants, all of whom had submitted abstracts concerning the issue discussed. The pertinent aspects of all issues discussed during the workshop are summarized. In addition, since the symposium was held over 2 yr ago, an addendum summarizing additional data reported since the symposium that either support or refute issues discussed during the workshop also is included.

Fatty Acids, Unsaturated↗

Aflatoxin M1 contamination in commercial samples of milk and dairy products in Kuwait.

As part of the programme on monitoring of environmental contaminants in food stuff in Kuwait, 54 samples of fresh full cream and skimmed milk, powdered milk, yoghurt, and infant formula were analysed for aflatoxin M1 (AFM1) by HPLC following sample clean up using immuno-affinity columns. Of samples, 28% were contaminated with AFM1 with 6% being above the maximum permissible limit of 0.2 microgl(-1). Three fresh cow milk samples collected from a private local producer showed the highest level of 0.21 microg l(-1) AFM1. There was no contamination with AFM1 in powdered milk and infant formulas. These results show the necessity of a survey involving a larger number of milk and its products and suggest that presently the contamination of milk and milk products with AFM1 does not appear to be a serious health problem in Kuwait. Nevertheless, a continuous surveillance programme may be warranted to monitor regularly the occurrence of aflatoxins in the animal feeds responsible for current limited contamination and to note rapidly and worsening in the situation that may depend on market changes or on unfavourable climatic developments.

Aflatoxin M1↗

[Protection of mother's milk and ethics].

INTRODUCTION: In 1981, the World Health Assembly created the International Code for the Marketing of Breast Milk Substitutes. The WHO standards have been effective in Brazil since 1988. The purpose of this study was to verify the companies' compliance with these standards, especially to what concern health care professionals. METHODS: An exploratory research was carried out in 32 cities, interviewing 95 health professional. RESULTS: Here we describe results of interviews with health professionals and their relationship with companies. Promotion of infant formula through pediatricians is common, showing evident conflict of interest: financial support they got for their benefits might link their names to the companies (and the products) that direct or indirectly funded them. There is a conflict of interest each time a secondary intention changes professional attitude (for example, changing methodology, analysis or type of results to be published) favoring this, instead of a scientific approach. CONCLUSIONS: Both the Code and the Resolution, gathering several ethical rules, are apparently not sufficient to assess the possible conflict of interest and to impose ethical limits in the relationship paediatrician-infant formula companies. Policies to protect breastfeeding practices of commercial interest must be reviewed to include ethics.

Conflict of Interest↗

Increased poliovirus-specific intestinal antibody response coincides with promotion of Bifidobacterium longum-infantis and Bifidobacterium breve in infants: a randomized, double-blind, placebo-controlled trial.

To determine whether the size of the intestinal bifidobacterial population can influence the immune response to poliovirus vaccination in infants, we set up a randomized, placebo-controlled trial. From birth to 4 mo, infants were given a fermented infant formula (FIF) or a standard formula (placebo). Bifidobacteria were quantified monthly in infant stools. Antipoliovirus IgA response to Pentacoq was assessed before and 1 mo after the second vaccine injection. Thirty infants were randomized, and 20 completed the study (nine in the placebo group and 11 in the FIF group). Fecal bifidobacterial level was significantly higher with the FIF group at 4 mo of age (p=0.0498). Furthermore, B. longum/B. infantis carriage was higher at 4 mo in the FIF group (p=0.0399). Antipoliovirus IgA titers increased after Pentacoq challenge (p <0.001), and the rise was significantly higher in the FIF group (p <0.02). Antibody titers correlated with bifidobacteria, especially with B. longum/B. infantis and B. breve levels (p <0.002). Infants who harbored B. longum/B. infantis also exhibited higher levels of antipoliovirus IgAs (p <0.002). In conclusion, the present results indicate that antipoliovirus response can be triggered with a fermented formula that is able to favor intestinal bifidobacteria. Whether this effect on the immune system is achieved through the bifidogenic effect of the formula (mainly through B. longum/B. infantis and B. breve stimulation) or directly linked to compounds (i.e. peptides) produced by milk fermentation remains to be investigated.

Bifidobacterium↗

What is the role of medium-chain triglycerides in the management of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency?

Cardiomyopathy is common in infants with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Resolution of the cardiomyopathy can often be achieved by avoidance of fasting and changing from a conventional infant formula to one in which most long-chain fat is replaced by medium-chain triglycerides (MCT). It is uncertain whether the clinical improvement is due to the restriction of long-chain fat or whether the MCT have specific beneficial effects. To clarify this, the metabolic effects of MCT were examined in 5 patients. When given at around the level found in MCT-based infant formula, MCT had no effect on blood concentrations of ketone bodies, specific fatty acids or acylcarnitines. The present study cannot, however, exclude the possibility that MCT per se may have beneficial effects.

3-Hydroxyacyl CoA Dehydrogenases↗

Concentrations of granulocyte colony-stimulating factor in human milk after in vitro simulations of digestion.

Human milk contains proteins that survive digestion in the neonatal gastrointestinal tract. Our group and others have reported that granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine that influences neutrophil proliferation and differentiation, is present in human milk. We also reported that specific receptors for G-CSF are expressed on the villous enterocytes of neonates. However, the physiologic role of milk-borne G-CSF is not known. Thus, we sought to evaluate the capacity of human milk to protect G-CSF against proteolytic degradation after exposure to gastric secretions obtained from preterm (PT) and term (T) neonates at pH concentrations of 3.2, 5.8, and 7.4. Specifically, we examined degradation of 1) endogenous G-CSF in PT (n = 15) and T (n = 15) human milk; 2) recombinant human G-CSF (rhG-CSF) added to a protein-free buffer (n = 10, 5 PT and 5 T); and 3) rhG-CSF added to human milk (n = 12, 6 PT and 6 T), various commercially prepared infant formulas (n = 15), and cow's milk (n = 5). Endogenous G-CSF and rhG-CSF added to human milk resisted degradation at 1 and 2 h. However, when rhG-CSF was added to commercial formulas, >95% was degraded at 1 and 2 h at each pH level. Similarly, approximately 60% of rhG-CSF added to cow's milk was degraded at I and 2 h. We conclude that 1) endogenous G-CSF and rhG-CSF added to human milk are protected from degradation after exposure to gastric secretions at physiologic pH levels, 2) rhG-CSF added to infant formulas is not protected from degradation, and 3) it is likely that the G-CSF present in human milk is biologically available to the neonate.

Digestion↗