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Intratracheal application of recombinant surfactant protein-C surfactant to rabbits attenuates acute lung injury induced by intratracheal acidified infant formula.

UNLABELLED: Our aim in the current study was to determine whether recombinant surfactant protein-C (rSP-C) surfactant improves acute lung injury (ALI) induced by intratracheal acidified milk products. Twenty-eight rabbits were randomly divided into four groups. ALI was induced with intratracheal acidified infant formula (0.8 mL/kg, pH 1.8) in 3 groups. The control group received intratracheal acidified saline. Therapy groups received 1 of 2 doses of intratracheal rSP-C surfactant (0.5 or 2 SP-C mg/kg) 30 min after the acidified infant formula. The lungs were ventilated with 100% oxygen for 4 h after induction of ALI. Acidified infant formula dramatically reduced oxygenation and lung compliance, and increased resistance. Both doses of rSP-C improved the variables [mean PaO(2) (mm Hg) and compliance (mL/cm H(2)O) at 4 h: 61 and 0.4 for infant formula, 162 and 1.0 for small-dose rSP-C, and 152 and 1.2 for large-dose rSP-C, respectively; P < 0.05]. Pulmonary leukosequestration and edema, and severe morphological changes were attenuated by rSP-C treatment (ALI score: 14, 7, 7 in infant formula, small-dose rSP-C, and large-dose rSP-C; P < 0.05). The efficacy was similar for the two doses of rSP-C. These findings suggest that intratracheal administration of rSP-C ameliorates ALI induced by aspiration of acidified milk products. IMPLICATIONS: Small or large doses of recombinant surfactant protein-C surfactant given 30 min after intratracheal acidified infant formula attenuated physiological, biochemical, and morphological lung damage.

Airway Resistance↗

Quantitative determination of complex carbohydrates in bovine milk and in milk-based infant formulas.

Quantitative determination of all structural families of complex carbohydrate micronutrients was performed on bovine milk samples, milk-based infant formulas, and whey-based manufacturing raw materials. Differences found between formulas depended mainly on their whey: casein ratios. A solvent separation procedure was required for quantitative estimation of the gangliosides and neutral glycolipids within the fat fraction. All infant formulas except one contained slightly more gangliosides than bovine milk. Complex carbohydrates were consistently higher in the nonfat fraction. By gel permeation chromatography, an oligosaccharide subfraction was separated from a glycopeptide one. Oligosaccharide content of infant formulas increased as a function of the whey:casein ratio, and glycopeptides were found only in formulas made with whey components. Neuraminic acids from infant formulas were associated primarily with the glycoprotein fraction, except in hydrolysate-based preparations in which "precipitable" glycoproteins were converted into "soluble" glycopeptides by trypsin treatment. Because whey-based raw materials are very rich in all bovine milk glycoconjugates and oligosaccharides their increased use will result in high contents of these micronutrients in modern formulas.

Animals↗

Effect of infant formula on stool characteristics of young infants.

BACKGROUND: Many infants are switched between multiple formula preparations early in life because of perceived abnormalities in stooling pattern as well as gastrointestinal symptoms. OBJECTIVE: To investigate the relationship between the type of formula consumed and the stooling characteristics and gastrointestinal symptoms of young infants. METHODS: Healthy 1-month-old infants were fed one of four commercial formula preparations (Enfamil, Enfamil with Iron, ProSobee, and Nutramigen) for 12 to 14 days in a prospective double-blinded (parent/physician) fashion. Parents completed a daily diary of stool characteristics as well as severity of spitting, gas, and crying for the last 7 days of the study period. A breast-fed infant group was studied as well. RESULTS: Two hundred eighty five infants were enrolled and 238 completed the study. Infants receiving breast milk or Nutramigen had twice as many stools as other formula groups (P < .001). Infants receiving ProSobee had hard/firm stools more often than breast-fed or other formula-fed groups (P < .00001). Watery stools were more common in infants fed Nutramigen than other formula groups (P < .04). Green stools were more common in 12 mg/L iron preparations (Enfamil with iron, ProSobee, Nutramigen) than in those with 1 mg/L (Enfamil, breast milk) (P < .00001). Spitting, gassiness, and crying were of equal severity in all formula groups. CONCLUSIONS: The interpretation of stool frequency, color, and consistency must take into account the infant's formula type as significant variations in normal infants occur. Parental education on the range of infant stooling characteristics as well as the common occurrence of spitting, gas, and crying may alleviate concern for formula intolerance and underlying gastrointestinal disease.

Analysis of Variance↗

Simultaneous quantification of vitamins A, D3 and E in fortified infant formulae by liquid chromatography-mass spectrometry.

A novel method for the simultaneous quantification of Vitamins A, D3 and E in fortified infant formulae has been developed using isocratic normal-phase liquid chromatography with positive atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS). Food products were saponified and the vitamins were extracted by solid-phase extraction (SPE) on a Chromabond XTR cartridge. Quantification of Vitamins D3 and E were performed with Vitamin D2 and 5,7-dimethyltocol (DMT) as internal standards (IS), respectively while no IS was used for Vitamin A. Detection of the vitamins was made in the selected ion monitoring (SIM) mode. MS calibration curves were linear between 0.15 and 12 mg/l for Vitamin A, 5-400 microg/l for Vitamin D3 and 0.25-20 mg/l for Vitamin E with regression coefficient r2 > 0.996 and the limits of detection were below 1.4 ng. The repeatability (CV) obtained on a reference dietetic infant formula was 2.3% for Vitamin A, 2.6% for Vitamin E and 5.9% for Vitamin D3. The between-day variations (CV) over 6 days were in the ranges of 2.4-6.9% for the three vitamins. The mean recoveries from a reference infant formula spiked with all three vitamins ranged from 96 to 105% with a relative standard error less than 9%. The applicability of the method was demonstrated by analyzing a set of infant formula and infant cereals; similar results were obtained with the LC-MS method and reference HPLC methods.

Cholecalciferol↗

Aluminum contents of human milk, cow's milk, and infant formulas.

BACKGROUND: Aluminum toxicity is well documented and contamination of milk formulas has been implicated as the source of accumulation in bone and brain tissues. The purpose of the current study was to evaluate the aluminum contents of human milk, cow's milk, and infant formulas. METHODS: Aluminum contents were determined by atomic absorption spectrometry in samples of human milk in the colostrum, intermediate, and mature stages; infant formulas from eight manufacturers; and various types and brands of commercially available cow's milk. RESULTS: Mean aluminum concentration was lowest in human milk (23.4 +/- 9.6 microg/l), and did not differ significantly between colostrum, intermediate-stage and mature-stage milk. Mean aluminum concentration was 70 microg/l in cow's milk, and 226 microg/l in reconstituted infant formulas. Aluminum concentrations in infant formulas differed markedly among manufacturers; concentration in milk from one of the manufacturers was particularly high (mean, 551 microg/l; range, 302-1149 microg/l). These values are for milk reconstituted with aluminum-free water under laboratory conditions; formulas prepared with tap water in the University Hospital's infant-feeding unit had even higher aluminum content. Experiments showed that aluminum concentration in the high-aluminum milk could be reduced by more than 70% at the manufacturing stage, by using low aluminum components. CONCLUSIONS: The results of the present study support the recommendations for infant formula manufacturers to strive to reduce aluminum concentration in their products.

Aluminum↗

Simultaneous determination of vitamins B2 (riboflavin) and B6 (pyridoxine) in infant formula products by reverse phase liquid chromatography.

An ion pair liquid chromatographic (LC) method is described for the simultaneous determination of vitamins B2 and B6 in infant formula products. The method eliminates many of the UV absorbing ingredients present in the infant formulations. The method involves extraction of the vitamins with distilled water followed by a filtration step and the subsequent analysis of the filtrate by LC. Vitamins B2 and B6 and their vitamers are separated from each other as well as from ingredients in the sample matrix on a 5 microns Spherisorb ODS column. The mobile phase consists of 85% 0.04 M triethylammonium phosphate (pH 3.0), 10% methanol, 5% acetonitrile, and the counter ion, octane sulfonic acid sodium salt. The method is reproducible for both vitamins with relative standard deviations (RSD) ranging from +/- 0.3 to +/- 2.6% depending on the infant formula product. The recoveries of the vitamins from various infant formula products are greater than 97%. The analysis for vitamins B2 and B6 in various lots of infant formula compared well with the official AOAC methods.

Chemical Phenomena↗

The protective effect of breast feeding in relation to sudden infant death syndrome (SIDS): I. The effect of human milk and infant formula preparations on binding of toxigenic Staphylococcus aureus to epithelial cells.

Epidemiological studies indicate that breast-fed infants are at a decreased risk of sudden infant death syndrome (SIDS) compared to formula-fed infants. Increasing evidence suggests that infectious agents might be involved in some of these deaths, in particular bacteria which colonise mucosal surfaces and produce superantigenic toxins. One species implicated in recent studies of SIDS infants is Staphylococcus aureus. We tested the hypothesis that in comparison to infant formula, human milk might be a better inhibitor of binding of S. aureus to epithelial cells. In this study, two protocols were used for the binding assays which were assessed by flow cytometry: the in vitro method in which bacteria were treated with milk or formula, washed and added to epithelial cells; and a method more closely reflecting the competitive interactions in vivo in which cells, bacteria, and milk or infant formula were added at the same time. With the in vivo method, breast milk caused enhancement of bacterial binding to cells whilst infant formula caused inhibition; however, for the in vitro method, both human milk and infant formula caused consistent enhancement of binding. Flow cytometry and light microscopy studies indicated that the enhancement was due to the formation of bacterial aggregates. Human milk and infant formula preparations were also compared for components (antibodies or oligosaccharides) that could inhibit binding of S. aureus using the in vitro method. Human milk contained both IgA and IgG. Neither human milk nor infant formula contained oligosaccharides reactive with the Ulex europaeus lectin but both contained components that bound monoclonal antibodies to Lewis(a) and Lewis(b) antigens which can act as receptors for S. aureus. With both methods, synthetic Lewis(a) and Lewis(b) inhibited S. aureus binding in a dose-dependent manner. With human milk, however, the only component which showed a significant correlation with inhibition of binding was the IgA specific for the staphylococcal surface component that binds Lewis(a). Both human milk and infant formula contain components which could potentially inhibit bacterial binding but only breast milk contains the IgA specific for the bacterial adhesin that binds Lewis(a). Studies using the in vivo method suggest that protection associated with breast feeding in relation to SIDS could be due mainly to the formation of bacterial aggregates. The studies have implications for further research into constituents of infant formula.

Adult↗

Influence of soya-based infant formula consumption on isoflavone and gut microflora metabolite concentrations in urine and on faecal microflora composition and metabolic activity in infants and children.

The urinary excretion of soya isoflavones and gut microflora metabolites was investigated in infants and children who had been fed soya-based infant formulas in early infancy. These infants and children were compared with cows'-milk formula-fed controls, to determine at what age gut microflora metabolism of daidzein to equol and/or O-desmethylangolensin (O-DMA) was established, and whether exposure to isoflavones in early infancy influences their metabolism at a later stage of development. Sixty infants and children (aged 4 months-7 years) participated in the study; thirty in each of the soya and control groups. There were four age groups. These were: 4-6 months (seven in the soya group and seven in the control group); 7-12 months (seven in the soya group and nine in the control group); 1-3 years (six in the soya group and eight in the control group); 3-7 years (ten in the soya group and six in the control group). Urine samples were collected to measure isoflavonoids by MS, and faecal samples were collected to measure gut-health-related bacterial composition, by fluorescent in situ hybridisation with oligonucleotide probes, and metabolic activity. A soya challenge (typically a soya yoghurt alternative product containing 4.8 g soya protein and on average 22 mg total isoflavones) was given to control-group infants (>6 months) and children, and also to soya-group children that were no longer consuming soya, to determine their ability to produce equol and/or O-DMA. Urinary genistein, daidzein and glycitein were detected in all infants (4-6 months) fed soya-based infant formula; O-DMA was detected in 75 % of infants but equol was detected in only 25 %. In the controls (4-6 months), urinary isoflavonoids were very low or not detected. In the older age groups (7 months-7 years), O-DMA was found in the urine samples of 75 % of the soya group and 50 % of the controls, after the soya challenge. Equol excretion was detected in 19 % of the soya-group infants and children, and in only 5 % of the controls. However, in the oldest (3-7 years) children, the proportion excreting O-DMA and equol was similar in both groups. Faecal bacterial numbers for bifidobacteria (P<0.001), bacteroides and clostridia (P<0.05) were significantly lower for the soya group compared with the control group. There appears to be no lasting effect of early-life isoflavone exposure on isoflavone metabolism.

Aging↗

Liquid chromatographic determination of vitamins D2 and D3 in fortified milk and infant formulas.

A liquid chromatographic (LC) method was developed for determining vitamins D2 and D3 in fortified milk and infant formulas. The lipid-soluble components were extracted from the aqueous phase by homogenizing in isopropanol-methylene chloride with magnesium sulfate added to remove water. The vitamins were fractionated from the lipid material by using gel permeation chromatography (GPC) followed by further cleanup of the combined GPC fractions on a muBondapak/NH2 column. Four muStyragel (100 A) columns connected in series were used for GPC fractionation of sample extracts in methylene chloride. Injection and collection were repeated 3 times to collect enough vitamin D for quantitation. The muBondapak/NH2 column, using a mobile phase of methylene chloride-isooctane-isopropanol (600 + 400 + 1), resolved vitamin D from other UV-absorbing compounds and soy sterols in infant formula and from cholesterol in milk. Vitamins D2 and D3 coeluted as one peak, with the resolution and vitamin level sufficient for visual monitoring (280 nm/0.02 absorbance unit full scale) in a collection time of 22-26 min. A Zorbax ODS (6 micron) column and a methylene chloride-acetonitrile-methanol (300 + 700 + 2) mobile phase were used for LC quantitation; vitamins D2 and D3 were baseline resolved in about 11 min. The infant formula samples included ready-to-use and concentrated liquids prepared in nonfat milk base or soy base fortified with vitamins D2 or D3 at 400 IU/qt or L (10 micrograms). The mean percent recovery of added vitamin D3 (400-500 IU/qt) from infant formula (n = 7) was 89.6 +/- 6.7 (coefficient of variation (CV) 7.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Safety of soy-based infant formulas containing isoflavones: the clinical evidence.

Soy protein has been used in infant feeding in the West for nearly 100 y. Soy protein infant formulas have evolved in this interval to become safe and effective alternatives for infants whose nutritional needs are not met with human milk or formulas based on cow's milk. Modern soy formulas meet all nutritional requirements and safety standards of the Infant Formula Act of 1980. They are commonly used in infants with immunoglobulin E-mediated cow's milk allergy (at least 86% effective), lactose intolerance, galactosemia, and as a vegetarian human milk substitute. Largely as a result of research in animal models, concerns have been voiced regarding isoflavones in soy infant formulas in relation to nutritional adequacy, sexual development, neurobehavioral development, immune function, and thyroid disease. We discuss the available clinical evidence regarding each of these issues. Available evidence from adult human and infant populations indicates that dietary isoflavones in soy infant formulas do not adversely affect human growth, development, or reproduction.

Animals↗

Selenium contents of human milk and infant formulas in Spain.

The selenium content of Spanish human milk samples and different milk-based and soy-based infant formulas has been estimated by using a flow injection hydride atomic absorption spectrometric method after microwave digestion of the organic matter. Mean values of 11.4 +/- 3.7 and 10.7 +/- 4.6 ng/ml for colostrum and transitional milk, 8.4 +/- 3.4 and 5.3 +/- 1.9 ng/ml for mature milk at 1 month and up to 2 months respectively, was obtained. These values are close to those reported by others authors in Europe, and lower than the ones from the US, Japan and Korea. Selenium contents of the analyzed infants' formulas ranged from 2.7 to 9.6 ng/ml and from 1.8 to 7.5 ng/ml for soy and milk-based infant formulas, respectively. The variability in selenium contents is large, although mean values are close to the ones given in other European countries. Selenium contents are not usually given on the product. The selenium intakes were estimated assuming that infants fed only human milk. The intakes ranged from 2.0 to 8.4 micrograms/day and from 3.4 to 12.9 micrograms/day for colostrum and transitional milk, respectively, and from 2.6 to 10.3 micrograms/day for mature milk at 1 month, and from 1.2 to 8.3 micrograms/day for milk up to 2 months. The analyzed infant formulas provide significantly less selenium than the 10 micrograms/day corresponding to the recommended daily allowance for infants from 0 to 6 months.

Animals↗

Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life.

Soy-based infant formulas have been in use for >30 y. These formulas are manufactured from soy protein isolates and contain significant amounts of phytoestrogens of the isoflavone class. As determined by HPLC, the isoflavone compositions of commercially available formulas are similar qualitatively and quantitatively and are consistent with the isoflavone composition of soy protein isolates. Genistein, found predominantly in the form of glycosidic conjugates, accounts for >65% of the isoflavones in soy-based formulas. Total isoflavone concentrations of soy-based formulas prepared for infant feeding range from 32 to 47 mg/L, whereas isoflavone concentrations in human breast milk are only 5.6 +/- 4.4 microg/L (mean +/- SD, n = 9). Infants fed soy-based formulas are therefore exposed to 22-45 mg isoflavones/d (6-11 mg x kg body wt(-1) x d(-1)), whereas the intake of these phytoestrogens from human milk is negligible (<0.01 mg/d). The metabolic fate of isoflavones from soy-based infant formula is described. Plasma isoflavone concentrations reported previously for 4-mo-old infants fed soy-based formula were 654-1775 microg/L (mean: 979.7 microg/L: Lancet 1997:350;23-7), significantly higher than plasma concentrations of infants fed either cow-milk formula (mean +/- SD: 9.4 +/- 1.2 microg/L) or human breast milk (4.7 +/- 1.3 microg/L). The high steady state plasma concentration of isoflavones in infants fed soy-based formula is explained by reduced intestinal biotransformation, as evidenced by low or undetectable concentrations of equol and other metabolites, and is maintained by constant daily exposure from frequent feeding. Isoflavones circulate at concentrations that are 13,000-22,000-fold higher than plasma estradiol concentrations in early life. Exposure to these phytoestrogens early in life may have long-term health benefits for hormone-dependent diseases.

Adult↗

Inactivation of Enterobacter sakazakii in reconstituted infant formula by monocaprylin.

Enterobacter sakazakii is an emerging pathogen that causes meningitis, bacteremia, sepsis, and necrotizing enterocolitis in neonates and children, with a mortality rate of 14%. Epidemiological studies have implicated dried infant formula as the principal source of the pathogen. Caprylic acid is a natural eight-carbon fatty acid present in breast milk and bovine milk and is approved as generally recognizable as safe by the U.S. Food and Drug Administration. The objective of this study was to determine the antibacterial effect of monocaprylin (monoglyceride ester of caprylic acid) on E. sakazakii in reconstituted infant formula. A five-strain mixture of E. sakazakii was inoculated into 10-ml samples of reconstituted infant formula (at 6.0 log CFU/ml) followed by 0, 25, or 50 mM (1%) monocaprylin. The samples were incubated at 37 or 23 degrees C for 0, 1, 6, and 24 h and at 8 or 4 degrees C for 0, 6, 24, and 48 h, and the surviving populations of E. sakazakii at each sampling time were counted. The treatments containing monocaprylin significantly reduced the population of E. sakazakii (P < 0.05) compared with the controls. Monocaprylin (50 mM) reduced the pathogen by >5 log CFU/ml by 1 h of incubation at 37 or 23 degrees C and by 24 h of incubation at 8 or 4 degrees C. Results indicate that monocaprylin could potentially be used to inactivate E. sakazakii in reconstituted infant formula; however, sensory studies are warranted before its use can be recommended.

Anti-Bacterial Agents↗

Milk from mothers of both premature and full-term infants provides better antioxidant protection than does infant formula.

We hypothesized that premature (PT) infants' mother's milk may provide antioxidant advantages compared with milk from mothers of full-term (FT) infants, and human milk may provide antioxidant properties not seen in infant formulas. We designed three experiments to test these hypotheses. Experiment 1 assessed resistance to oxidative stress of human milk and formulas designed for FT and PT infants. Experiment 2 determined differences in resistance to oxidative stress between milk from mothers of FT and PT infants, including analysis of catalase activity. Experiment 3 examined factors in human milk that may account for increased resistance to oxidative stress. In experiment 1, we induced physiologic oxidative stress in human milk (n = 5) and formula (n = 2) and measured ascorbate radical using electron paramagnetic resonance. Results indicated the following: 1) during oxidative stress, ascorbate may be spared in human milk compared with formula; 2) ascorbate radical production is more intense in formula compared with human milk, with or without oxidative stress; and 3) oxygen consumption in human milk is less than that in formula, with or without oxidative stress. In experiment 2, milk samples were collected from mothers of PT (n = 28) and FT (n = 17) infants at wk 1, 2, and 12 of lactation. No differences in oxygen consumption after oxidative stress appeared between PT and FT milk. Catalase levels in human milk increased with time. In experiment 3, addition of catalase, superoxide dismutase, and glutathione peroxidase to formulas (n = 4) increased resistance to oxidative stress. Denaturing endogenous enzymes did not decrease the ability of human milk to resist oxidative stress. Ferrous sulfate plus vitamin C added to human milk and formulas fortified with iron increased oxidative stress. Addition of iron chelators to formula reduced oxidative stress. In conclusion, human milk has better antioxidant protection than do formulas, perhaps because of the higher iron content of formulas. Milk from mothers of PT and FT infants has equal resistance to oxidative stress.

Antioxidants↗

Lactoferrin in infant formulas: effect on oxidation.

Lactoferrin is an iron transport protein present in human milk at an average concentration of 1.4 mg/mL. Commercially modified infant formulas based on cow's milk contain much lower amounts of lactoferrin (0.1 mg/mL lactoferrin) and soy based formulas have none. In addition to its role in iron transport, lactoferrin has bacteriostatic and bactericidal activities. Infant formulas are supplemented with relatively large amounts of iron (up to 12 mg/L). The effect of various concentrations of added lactoferrin and supplemental iron on lipid oxidation was tested in two different infant formulas. The extent of oxidation in the formulas as a function of time was determined by formation of hydroperoxides, production of hexanal, and fluorescence. On the basis of all three of these determinations, lactoferrin acted as an antioxidant in the absence and presence of different concentrations of supplemented iron. Lactoferrin inhibited oxidation in a concentration-dependent manner even at concentrations beyond its capacity to bind iron at its two high affinity binding sites. Lactoferrin can be used, therefore, as a dual purpose additive in infant formulas and similar food products for its antioxidant and its antimicrobial properties.

Humans↗

Determination of proteins in infant formula by high-performance liquid chromatography-electrospray tandem mass spectrometry.

To determine the protein content of formula, gel electrophoresis was performed on the infant formula samples and the entire protein patterns were analyzed by nano-high performance liquid chromatography-electrospray tandem mass spectrometry (nano-HPLC/ESI/MS/MS). From the commercial infant formula profiled in this study, a total of 154 peptides, corresponding to 31 unique proteins were identified by nano-HPLC/ESI/MS/MS. Each of the identified peptides was reconfirmed by a strict integrated approach using tandem mass spectra. This protein profiling method using gel electrophoresis coupled with nano-HPLC/ESI/MS/MS and manual evaluation is a sensitive and accurate method for protein identification as well as a powerful tool for monitoring various types of food products.

Chromatography, High Pressure Liquid↗

Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial.

BACKGROUND: We tested whether addition of n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) to infant-formula milk during the first 6 months promotes long-term cognitive and motor development, without adverse consequences. METHODS: We did a double-blind, randomised, controlled, efficacy and safety trial of formula with and without LCPUFAs, with an additional breastfed reference group, in four hospitals in two cities in the UK. The participants were 447 healthy full-term babies. 309 were fed formula (155 without LCPUFAs) and 138 were breastfed for at least 6 weeks. The main outcome measures were: Bayley Mental and Psychomotor Development Indices (MDI, PDI) at 18 months (primary efficacy outcome) and Knobloch, Passamanick, and Sherrards test at 9 months (secondary outcome). Principal safety outcomes were: infection, atopy, growth, and gastrointestinal tolerance. FINDINGS: Babies fed formula with and without LCPUFA did not differ in cognitive or motor development, growth, infection, atopy or tolerance. The mean (95% CI) MDI was 0.5 (-2.7 to 3.8) units and the PDI 0.6 (-1.8 to 3.0) units higher in the supplementation group. Formula-fed infants had similar developmental scores to the breastfed reference group after adjustment for higher social class and maternal education in the latter. INTERPRETATION: There was no evidence of a beneficial or adverse effect on cognitive and motor development or growth up to 18 months. Although no significant differences in safety outcomes were observed, we suggest such data should be collected in future LCPUFA trials. Our trial does not provide support for addition of LCPUFA to standard infant formula but we are now doing further follow-up of this cohort.

Animals↗

Risk factors for enamel fluorosis in optimally fluoridated children born after the US manufacturers' decision to reduce the fluoride concentration of infant formula.

This case-control study investigated risk factors for enamel fluorosis in optimally fluoridated children, born after the US infant formula industry voluntarily reduced the fluoride content of their products. Analysis was performed on 233 children, aged 10-14 years. Case-control status was determined using the Fluorosis Risk Index (FRI). Risk factor exposure was ascertained via a mailed questionnaire. Logistic regression analyses revealed a strong association between mild-to-moderate enamel fluorosis on early forming (FRI classification I) enamel surfaces and both fluoride supplement use (odds ratio (OR)=5.95, 95% confidence interval (CI) 1.06-33.53), and early fluoride toothpaste use (OR=6.35, 95% CI 1.21-33.40). The authors found a suggestive, but nonsignificant, association between fluorosis on these enamel surfaces and infant formula in the form of powdered concentrate (OR=4.33, 95% CI 0.73-25.66). There was a strong association between mild-to-moderate fluorosis on later forming (FRI classification II) enamel surfaces and infant formula use in the form of powdered concentrate (OR=10.77, 95% CI 1.89-61.25), fluoride supplement use (OR=10.83, 95% CI 1.90-61.55), and early fluoride toothpaste use (OR=8.37, 95% CI 1.68-41.72). No association was observed between the use of ready to feed infant formula and enamel fluorosis.

Adolescent↗