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Background: Breastfeeding is associated with a variety of positive health outcomes in children and is recommended exclusively for the first 6 months of life; however, 50-70 % of infants in the US are formula-fed. To test the hypothesis that immune system development and function in neonates and infants are significantly influenced by diet, 2-day old piglets were fed soy or milk formula (n = 6/group/gender) until day 21 and compared to a sow-fed group (n = 6/gender)., Methods: Histomorphometric analyses of ileum, jejunum and Peyer's patches were carried out, to determine the inflammation status, mRNA and protein expression of pro-inflammatory, anti-inflammatory and growth-related chemokines and cytokines., Results: In formula-fed animals, increases in ileum and jejunum villus height and crypt depth were observed in comparison to sow-fed animals (jejunum, p < 0.01 villus height, p < 0.04 crypt depth; ileum p < 0.001 villus height, p < 0.002 crypt depth). In formula-fed the lymphoid follicle size (p < 0.01) and germinal centers (p < 0.01) with in the Peyer's patch were significantly decreased in comparison to sow-fed, indicating less immune education. In ileum, formula diet induced significant up-regulation of AMCFII, IL-8, IL-15, VEGFA, LIF, FASL, CXCL11, CCL4, CCL25 and down-regulation of IL-6, IL-9, IL-10, IL-27, IFNA4, CSF3, LOC100152038, and LOC100736831 at the transcript level. We have confirmed some of the mRNA data by measuring protein, and significant down-regulation of anti-inflammatory molecule IL-10 in comparison to sow-fed piglets was observed. To further determine the membrane protein expression in the ileum, VE-cadherin, occludin, and claudin-3, Western blot analyses were conducted. Sow fed piglets showed significantly more VE-Cadherin, which associated with levels of calcium, and putrescine measured. It is possible that differences in GI tract and immune development are related to shifts in the microbiome; notably, there were 5-fold higher amounts of Lactobacillaceae spp and 3 fold higher Clostridia spp in the sow fed group in comparison to milk formula-fed piglets, whereas in milk formula-fed pigs Enterobacteriaceae spp was 5-fold higher., Conclusion: In conclusion, formula diet alters GI morphology, microbial abundance, intestinal barrier protein VE-cadherin and anti-inflammatory molecule IL-10 expression. Further characterization of formula effects could lead to modification of infant formula to improve immune function, reduce inflammation and prevent conditions such as allergies and infections.

Unlabelled: Effects of the dietary glycaemic load on postprandial blood glucose and insulin response might be of importance for fat deposition and risk of obesity. We aimed to investigate the metabolic effects, acceptance and tolerance of a follow-on formula containing the low glycaemic and low insulinaemic carbohydrate isomaltulose replacing high glycaemic maltodextrin. Healthy term infants aged 4 to 8 completed months (n = 50) were randomized to receive the intervention follow-on formula (IF, 2.1g isomaltulose (Palatinose™)/100mL) or an isocaloric conventional formula (CF) providing 2.1g maltodextrin/100mL for four weeks. Plasma insulinaemia 60 min after start of feeding (primary outcome) was not statistically different, while glycaemia adjusted for age and time for drinking/volume of meal 60 min after start of feeding was 122(105,140) mg/dL in IF (median, interquartile range) and 111(100,123) in CF (p = 0.01). Urinary c-peptide:creatinine ratio did not differ (IF:81.5(44.7, 96.0) vs. CF:56.8(37.5, 129),p = 0.43). Urinary c-peptide:creatinine ratio was correlated total intake of energy (R = 0.31,p = 0.045), protein (R = 0.42,p = 0.006) and fat (R = 0.40,p = 0.01) but not with carbohydrate intake (R = 0.22,p = 0.16). Both formulae were well accepted without differences in time of crying, flatulence, stool characteristics and the occurrence of adverse events. The expected lower postprandial plasma insulin and blood glucose level due to replacement of high glycaemic maltodextrin by low glycaemic isomaltulose were not observed in the single time-point blood analysis. In infants aged 4 to 8 completed months fed a liquid formula, peak blood glucose might be reached earlier than 60 min after start of feeding. Non-invasive urinary c-peptide measurements may be a suitable marker of nutritional intake during the previous four days in infants., Trial Registration: ClinicalTrials.gov NCT01627015.

Dental caries are a major public health problem worldwide. The aim of this study was to compare the effects of children's follow-on instant powdered cow's milk formula, buffalo milk formula and a chicken-based formula on microhardness of bovine enamel with artificial caries-like lesions. Forty bovine teeth were each placed in acrylic blocks and the enamel surfaces were polished to create flat 5 x 5 millimeter surfaces. The teeth surfaces were then demineralized using 0.1M lactic acid (pH 4.5) to achieve an enamel microhardness of 35-65 Vickers Hardness Numbers (VHN). All specimens were then randomly allocated into one of 4 groups (n=10/group). For remineralization, each group was soaked in a different kind of milk formula for 2 hours at 37°C except group 1 which was a negative control (artificial saliva) group. Group 2 was soaked in Murrah™ buffalo milk formula (a positive control ), group 3 in S-26-Promil-Gold™ (cow's milk formula) and group 4 in a chicken-based formula (Siriraj Hospital, Mahidol University). The microhardness of the specimens was then measured again. Data were analyzed using a one-way ANOVA and paired t-test with a 95% confidence interval. After exposure to the formula, the mean VHN for each study group was significantly higher (paired t-test, p < 0.05) except for group 1 (p = 0.345). The mean VHN for the the Murrah™ buffalo milk formula, the chicken-based formula and the S-26-Promil-Gold™ formula group were not significantly different from each other (one-way ANOVA, p > 0.05). In conclusion, S-26-Promil-Gold™ follow-on cow milk formula, Murrah™ buffalo milk formula and the chicken-based formula all increased bovine enamel microhardness after soaking for 2 hours.

l-Fucose is a natural monosaccharide present in mammals where it is found predominantly as an O-glycosidically linked component of glycoproteins, glycolipids, and oligosaccharides. It is also present in its free form in human breast milk (human milk monosaccharide). l-Fucose plays important roles in the development of the immune and nervous systems and is involved in cognitive function and memory formation. The human-identical milk monosaccharide l-fucose is therefore proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of l-fucose, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague-Dawley rats. l-Fucose was without maternal toxicity or compound-related adverse effects on female reproduction and general growth and development of offspring at a maternal dietary level up to 1%, equivalent to a dose of 1655 mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 1% (highest level tested), corresponding to doses of 516 and 665 mg/kg bw/day in males and females, respectively. l-Fucose was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of l-fucose in infant formula and as a food ingredient at levels equivalent to those present in human breast milk., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: To evaluate the impact of oligofructose (OF)-supplemented infant formula on fecal microbiota, stool characteristics, and hydration., Methods: Ninety-five formula-fed infants were randomized to α-lactalbumin-enriched control formula (CF) or identical formula with 3.0 g/L OF (EF) for 8 weeks; 50 infants fed human milk (HM) were included., Results: Eighty-four infants completed the study, 70 met per-protocol criteria. Over 8 weeks, bifidobacteria increased more in EF than CF group (0.70 vs. 0.16 log10 bacterial counts/g dry feces, P = .008); EF was not significantly different from HM group (P = .32). EF group stool consistency was intermediate between CF and HM groups; at week 8, EF group had softer stools than CF (5-point scale: 1 = hard, 5 = watery; consistency score 3.46 vs. 2.82, P = .015) without significant differences in stool frequency. Physician-assessed hydration status was normal for all infants., Conclusions: Infant formula with 3.0 g/L OF promoted bifidobacteria growth and softer stools without adversely affecting stool frequency or hydration., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Susan Wernimont, Robert Northington, Manjiang Yao, and Jodi Bettler are employees of Nestlé Nutrition. Martin Kullen was an employee of Wyeth Nutrition at the time of the study and is currently employed by DuPont Nutrition & Health, Wilmington, Delaware., (© The Author(s) 2014.)

Human milk is the gold standard for nourishment of early infants because it contains a number of bioactive components, such as human milk oligosaccharides (HMOs). The high concentration and structural diversity of HMOs are unique to humans. HMOs are a group of complex and diverse glycans that are resistant to gastrointestinal digestion and reach the infant colon as the first prebiotics. N-acetyl-glucosamine containing oligosaccharides were first identified 50 years ago as the 'bifidus factor', a selective growth substrate for intestinal bifidobacteria, thus providing a conceptual basis for HMO-specific bifidogenic activity. Bifidobacterial species are the main utilisers of HMOs in the gastrointestinal tract and represent the dominant microbiota of breast-fed infants, and they may play an important role in maintaining the general health of newborn children. Oligosaccharides are also known to directly interact with the surface of pathogenic bacteria, and various oligosaccharides in milk are believed to inhibit the binding of pathogens and toxins to host cell receptors. Furthermore, HMOs are thought to contribute to the development of infant intestine and brain. Oligosaccharides currently added to infant formula are structurally different from the oligosaccharides naturally occurring in human milk and, therefore, they are unlikely to mimic some of the structure-specific effects. In this review, we describe how HMOs can modulate gut microbiota. This article summarises information up to date about the relationship between the intestinal microbiota and HMOs, and other possible indirect effects of HMOs on intestinal environment.

Relatively high amounts of protein are required to achieve normal fractional protein synthetic rates during the late second through early third trimester of fetal growth. Once preterm infants achieve higher protein intakes for sustained periods, growth begins to approximate that of the normally growing fetus and long-term neurodevelopmental outcomes are improved. Preterm formulas have been developed that are enriched in protein. This review discusses several factors when using standard preterm formulas and high-protein preterm formulas in the neonatal intensive care unit, with an emphasis on quantity and quality of enteral protein delivery and risks to insufficient and/or excess protein administration., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The rapid expansion of commercially available fermented food products raises important safety issues particularly when infant food is concerned. In many cases, the activity of the microorganisms used for fermentation as well as what will be the immunological outcome of fermented food intake is not known. In this manuscript we used complex in vitro, ex-vivo and in vivo systems to study the immunomodulatory properties of probiotic-fermented products (culture supernatant and fermented milk without live bacteria to be used in infant formula). We found in vitro and ex-vivo that fermented products of Lactobacillus paracasei CBA L74 act via the inhibition of proinflammatory cytokine release leaving anti-inflammatory cytokines either unaffected or even increased in response to Salmonella typhimurium. These activities are not dependent on the inactivated bacteria but to metabolic products released during the fermentation process. We also show that our in vitro systems are predictive of an in vivo efficacy by the fermented products. Indeed CBA L74 fermented products (both culture medium and fermented milk) could protect against colitis and against an enteric pathogen infection (Salmonella typhimurium). Hence we found that fermented products can act via the inhibition of immune cell inflammation and can protect the host from pathobionts and enteric pathogens. These results open new perspectives in infant nutrition and suggest that L. paracasei CBA L74 fermented formula can provide immune benefits to formula-fed infants, without carrying live bacteria that may be potentially dangerous to an immature infant immune system.

Background: Effects of palm olein (POL) on calcium and fat metabolic balance and gastrointestinal (GI) tolerance have been clinically evaluated but its use in combination with palm kernel oil (PKO), and canola oil has not been similarly assessed in infants., Methods: Calcium and fat balance and GI tolerance were evaluated in 33 healthy term infants (age = 68-159 d) in a randomized, double-blinded, 14 d crossover trial at a day care center in Salvador, Brazil; followed by a 4d hospital ward metabolic balance study in 17 of the male subjects. The study compared two commercially available milk-based powdered formulas in Brazil; one containing POL (44% of total fat), PKO (21.7%) and canola oil (18.5%) as predominant fats (PALM), and the other containing none (NoPALM). Occasional human milk (HM) supplementation was allowed at home., Results: Formula and HM intakes, and growth were not different (p > 0.05). Calcium absorption (%) for infants fed NoPALM (58.8 ± 16.7%; means ± SD) was higher (p = 0.023) than those fed PALM (42.1 ± 19.2%), but was not significant (p = 0.104) when calcium intake was used as a covariate. Calcium intake was higher (p < 0.001) in NoPALM versus PALM fed infants. However, calcium retention (%) was higher in infants fed NoPALM compared to PALM with (p = 0.024) or without (p = 0.015) calcium intake as a covariate. Fat absorption (%) for NoPALM was greater than PALM fed infants (NoPALM = 96.9 ± 1.2 > PALM = 95.1 ± 1.5; p = 0.020 in Study Period I). Mean rank stool consistency was softer in infants fed NoPALM versus PALM (p < 0.001; metabolic period). Adverse events, spit-up/vomit, fussiness and gassiness were not different (p > 0.05). Formula acceptability was high and comparable for both formula feedings, regardless of HM supplementation., Conclusions: Term infants fed PALM based formula (containing palm olein, palm kernel and canola oils) demonstrated lower calcium retention and fat absorption, and less softer stool consistency versus infants fed NoPALM based formula. Study suggested formula fat differences may affect GI function in infants.

Introduction: The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC)., Material and Methods: Newborn Sprague-Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression., Results: The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p<0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1., Discussion: Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Natural killer (NK) cells are components of the innate immune defense system, and their levels differ between breast and formula-fed (FF) infants. Lactoferrin (Lf) modulates NK cell cytotoxicity ex vivo. We hypothesized that dietary bovine Lf (bLf) would increase NK cell populations and cytotoxicity., Methods: Piglets were sow-reared (SR), FF, or 1 g/l bLf-fed (LF) for 21 d. NK cells (CD3(-)CD4(-)CD8(+)) in blood (peripheral blood mononuclear cells (PBMCs)), spleen, and mesenteric lymph node (MLN) were determined by flow cytometry. PBMC NK cells were tested for cytotoxic activity against target K562 cells ex vivo in the presence of media (unstimulated), interleukin-2, or bLf. NK cell mRNA expression was determined by reverse transcription-quantitative PCR., Results: SR and LF piglets had more NK cells in MLN (P = 0.0097) and spleen (P = 0.0980) than FF piglets. In PBMCs, SR piglets had more NK cells than FF piglets (P = 0.0072); LF piglets were intermediate and not different from FF or SR piglets. NK cell intelectin-2 mRNA expression was 2.5-fold higher (P = 0.0095) in LF than SR or FF piglets. NK cells in SR piglets exhibited greater (P < 0.0001) cytotoxic activity than those in LF or FF piglets, which was supported by greater perforin mRNA expression., Conclusion: Dietary bLf increased blood NK cell populations and NK Lf receptor expression but not NK cell cytotoxicity.

Background: The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood., Aims: We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes., Study Design and Subjects: 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined., Results: We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail., Conclusions: These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Gastro-esophageal reflux (GER) is diagnosed frequently in preterm infants. Pharmacological treatment of GER has some potential side effects. Conservative treatment of GER should be the first-line approach and should include body positioning and diet modifications. Formula-fed preterm infants experience frequently symptoms of feeding intolerance. Hydrolyzed protein formula (HPF) is often used in these infants due to their effects on gastrointestinal motility., Aims: To investigate the role of an extensively HPF (eHPF) on GER indexes in formula-fed preterm infants with symptoms of both GER and feeding intolerance., Study Design: Randomized crossover trial., Subjects: Preterm infants (gestational age ≤33 weeks) with symptoms of feeding intolerance (large gastric residuals, abdominal distension and constipation) and GER (frequent regurgitations and/or postprandial desaturations)., Outcome Measures: GER indexes detected by 24-h combined multichannel intraluminal impedance and pH monitoring. GER indexes detected after 4 feeds of an eHPF were compared to those detected after 4 feeds of a standard preterm formula (SPF) by Wilcoxon signed ranks test. A p<0.05 was considered statistically significant., Results: eHPF significantly reduced the number of GERs detected by pH monitoring (p=0.036) and also the reflux index (p=0.044) compared to SPF. No differences in impedance bolus exposure indexes nor in GER height were detected., Conclusions: The use of an eHPF should be evaluated for reducing esophageal acid exposure in preterm infants with feeding intolerance and symptoms of GER. Future research should focus on the evaluation of an eHPF adequate for preterm infants in improving clinical symptoms of GER., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by severe intestinal necrosis and for which breast milk represents the most effective protective strategy. Previous studies have revealed a critical role for the lipopolysaccharide receptor toll-like receptor 4 (TLR4) in NEC development through its induction of mucosal injury, yet the reasons for which intestinal ischemia in NEC occurs in the first place remain unknown. We hypothesize that TLR4 signaling within the endothelium plays an essential role in NEC development by regulating perfusion to the small intestine via the vasodilatory molecule endothelial nitric oxide synthase (eNOS). Using a unique mouse system in which we selectively deleted TLR4 from the endothelium, we now show that endothelial TLR4 activation is required for NEC development and that endothelial TLR4 activation impairs intestinal perfusion without effects on other organs and reduces eNOS expression via activation of myeloid differentiation primary response gene 88. NEC severity was significantly increased in eNOS(-/-) mice and decreased upon administration of the phosphodiesterase inhibitor sildenafil, which augments eNOS function. Strikingly, compared with formula, human and mouse breast milk were enriched in sodium nitrate--a precursor for enteral generation of nitrite and nitric oxide--and repletion of formula with sodium nitrate/nitrite restored intestinal perfusion, reversed the deleterious effects of endothelial TLR4 signaling, and reduced NEC severity. These data identify that endothelial TLR4 critically regulates intestinal perfusion leading to NEC and reveal that the protective properties of breast milk involve enhanced intestinal microcirculatory integrity via augmentation of nitrate-nitrite-NO signaling.

Background: Human milk is the gold standard of infant nutrition and is a source of important substances, including carotenoids. Infant formulas are designed to mimic the composition and/or performance of human milk, although currently carotenoids are not routinely added to US infant formulas. The aim of this study was to assess plasma concentrations of β-carotene, lutein and lycopene 56 days after feeding infants milk-based infant formula without (CTRL) or with different concentrations of added carotenoids (L1 and L2)., Results: Plasma carotenoid concentrations increased in infants fed carotenoid-supplemented formulas as compared with the control formula with no added carotenoids. At study day 56, infants fed the supplemented formulas (L1 and L2) had mean plasma lutein, β-carotene and lycopene concentrations that were within the range of a concurrent group of human milk-fed infants (HM). Anthropometric measurements were comparable among all study groups., Conclusion: Plasma carotenoid concentrations of infants fed the supplemented formulas were within the range of the HM group and are consistent with reported plasma carotenoid ranges in human milk-fed infants. The experimental formulas were well tolerated and anthropometric measurements were comparable among all study groups., (© 2012 Society of Chemical Industry.)

Since type 1 diabetes is an immunologically mediated disease, immune intervention should alter the natural history of the disease. This article reviews prevention studies undertaken either prior to any evidence of autoimmunity (primary prevention) or after the development of islet autoantibodies (secondary prevention). Most immune intervention studies have been conducted in recent-onset type 1 diabetes (tertiary prevention), and these are not reviewed herein. The goal of primary and secondary intervention is to arrest the immune process and thus prevent or delay clinical disease. Primary prevention studies have been conducted in infants with high genetic risk. Interventions tested include several dietary manipulations, including infant formulas free of either cow's milk or of bovine insulin, infant formula supplemented with the omega-3-fatty acid docosahexaenoic acid, delayed introduction of gluten-containing foods, and vitamin D supplementation. Secondary prevention studies have been conducted in both children and adults with diabetes autoantibodies. Interventions tested include nicotinamide, insulin injections, oral insulin, nasal insulin, glutamic acid decarboxylase, and cyclosporine. Underway are secondary prevention studies with teplizumab and with abatacept., (© 2012 The Author. Diabetic Medicine © 2012 Diabetes UK.)

Aim: Long-chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years. Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy., Method: A double-blind, randomized control study was performed in two groups of healthy infants born at term: one group, constituting the control group, received standard formula (n=169) and another group received standard formula supplemented with LCPUFAs (n=146). A breastfed group (n=159) served as an additional reference. At 9 years of age, 72% of the children (control group: n=123; 71 males, 52 females; LCPUFA group: n=91; 42 males, 49 females; breastfed group: n=127, 64 males, 63 females) underwent extensive cognitive and behavioural testing., Results: An interaction between infant nutrition and smoking during pregnancy was found. Among children exposed to smoking during pregnancy, LCPUFA supplementation was associated with higher mean verbal IQ scores (p=0.007) and learning and memory (p=0.006). Among children not exposed to smoking during pregnancy, LCPUFA supplementation was associated with lower mean verbal memory scores (p=0.003). Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group (p=0.001). Breastfeeding was associated with better performance on IQ (p=0.005)., Interpretation: No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found. The study confirmed that breastfeeding is associated with better cognition., (© The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.)

Polyamines play a critical role in the development of intestinal and immune systems during the infant breastfeeding period, but the effect of polyamines on the microbiota has not been reported. The aim of our study was to characterize the impact on the colonization pattern in neonatal BALB/cOlaHsd mice after supplementing an infant formula (IF) with a mixture of putrescine (PUT), spermidine (SPD) and spermine (SPM). A total of 48 pups (14 days old) were randomly assigned to 4-day intervention groups as follows: breast-fed (unweaned) pups (n=12); weaned pups (n=12) fed an infant formula (IF); weaned pups (n=12) fed an IF enriched with a low concentration of PUT, SPD and SPM (2.10, 22.05 and 38.00 μg/day, respectively); and weaned pups (n=12) fed with IF enriched with a high concentration of PUT, SPD and SPM (8.40, 88.20 and 152.00 μg/day, respectively) of polyamines in accordance with normal proportions found in human milk. Microbiota composition was analyzed by fluorescent in situ hybridization (FISH) with flow cytometry detection. Microbiota changes in formula-fed mice were significantly greater following supplementation with polyamines (P<.01). Bifidobacterium group bacteria, Akkermansia-like bacteria and Lactobacillus-Enterococcus group levels were higher in the groups fed infant formula supplemented with polyamines, resulting in even higher numbers of bacteria than in the breastfed pups. Our findings indicate that infant formulas enriched with polyamines may interact with gut microbiota, suggesting that further studies in human infants are required to assess the impact of polyamines on both growth and microbiota levels., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Human milk is the optimal nutrition for infants. When breastfeeding is not possible, supplementation of infant formula with long chain polyunsaturated fatty acids appears to promote neurodevelopmental outcome and visual function. Plant oils, that are the only source of fat in most of infant formulas, do not contain specific fatty acids that are present in human and cow milk and do not encounter milk fat triglyceride structure. Experimental data suggest that a mix of dairy lipids and plant oils can potentiate endogenous synthesis of n-3 long chain polyunsaturated fatty acids. This trial aims to determine the effect of an infant formula supplemented with a mixture of dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in full-term infants (primary outcome). Erythrocyte membrane long chain polyunsaturated fatty acids and fatty acids content, the plasma lipid profile and the insulin-growth factor 1 level, the gastrointestinal tolerance, the changes throughout the study in blood fatty acids content, in growth and body composition are evaluated as secondary outcomes., Methods/design: In a double-blind controlled randomized trial, 75 healthy full-term infants are randomly allocated to receive for four months a formula supplemented with a mixture of dairy lipids and plant oils or a formula containing only plant oils or a formula containing plant oils supplemented with arachidonic acid and docosahexaenoic acid. Twenty-five breast-fed infants constitute the reference group. Erythrocyte membrane omega-3 fatty acid profile, long chain polyunsaturated fatty acids and the other fatty acids content, the plasma lipid profile and the insulin-growth factor 1 level are measured after four months of intervention. Gastrointestinal tolerance, the changes in blood fatty acids content, in growth and body composition, assessed by means of an air displacement plethysmography system, are also evaluated throughout the study., Discussion: The achievement of an appropriate long chain polyunsaturated fatty acids status represents an important goal in neonatal nutrition. Gaining further insight in the effects of the supplementation of a formula with dairy lipids and plant oils in healthy full-term infants could help to produce a formula whose fat content, composition and structure is more similar to human milk., Trial Registration: ClinicalTrials.gov Identifier NCT01611649.

Purpose: This study was undertaken to assess the safety and efficacy of minimally invasive percutaneous nephrolithotomy (mini-PCNL) using ureteroscope and pneumatic intracorporeal lithotripsy in preschool age children with kidney calculi., Methods: We studied 27 renal units in 20 patients of preschool age (≤ 6 years) who underwent mini-PCNL at our institute. The mean age was 42.6 months (range 14-68 months). The average stone burden was 1.85 cm (range 0.9-2.8 cm). Eight patients aged 14 to 58 months had been exposed to melamine-tainted powdered formula. The mini-PCNL was performed with an X-ray-guided peripheral puncture. Minimal tract dilatation was undertaken to fit a 14-16 Fr peel-away sheath. Ureteroscope and pneumatic intracorporeal lithotripsy were used to fragment the stones., Results: Complete clearance was achieved in 23 renal units (85.2 %) with mini-PCNL monotherapy. This has increased to 92.6 % after adjunctive ESWL. The average fall in hemoglobin was 1.28 g/dL. None of the patients required blood transfusion. The median length of hospital stay was 8.2 days. Patients were followed up every 6 months for 2 years. There has been only one recurrence of stone and no long-term complications., Conclusion: Mini-PCNL is a effective treatment for pediatric kidney stones refractory to extracorporeal shock wave lithotripsy, including stones induced by melamine-contaminated milk powder. The "mini-PCNL" technique, which uses ureteroscope and pneumatic intracorporeal lithotripsy, is a safe and feasible modality for treating renal calculi in preschool age children.

Background: In preterm-born infants, low birth weight and diminished bone accretion deteriorate peak bone mass. Whether low birth weight is already associated with decreased bone mass during infancy is unknown., Objective: To study the effect of birth weight on bone accretion between term age (40 weeks postmenstrual age) and six months post-term in preterm-born infants., Design: In 139 preterm-born infants (51% male, gestational age 30.3±1.5 weeks, birth weight 1341±288g) weight and whole-body bone mineral content (BMC, gram) were measured at term age and six months post-term. At birth, infants were small-for-gestational-age (SGA, n=33, weight and/or length<-2 SDS) or appropriate-for-gestational-age (AGA, n=98, weight and length≥-2 SDS)., Results: At term age and six months post-term, BMC adjusted for gender and gestational age was lower in SGA than AGA infants (term age: 38.1±9.5 versus 48.6±10.1g, β=-0.26, 95% CI -0.37; -0.16, p<0.001; six months: 130.1±25.7 versus 145.4±22.9g, β=-0.16, 95% CI -0.25; -0.08, p<0.001). At six months post-term, BMC remained lower in SGA infants after adjustment for actual weight and length. Between term age and six months post-term, BMC gain adjusted for gender and gestational age was lower in SGA than AGA infants (91.7±22.8 versus 98.2±20.7g; β=-0.12, 95% CI -0.24; -0.003, p=0.044). BMC gain remained lower in SGA infants after adjustment for weight and length gain., Conclusion: The first six months post-term, SGA preterms have lower bone accretion, independent of body size, suggesting that prenatal conditions for bone accretion cannot be replicated postnatally., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Infants are vulnerable: their growth and their development depend largely on their nutritional status. It is important to propose for them an optimal food. The human milk is unquestionably the best choice for the infant. When breastfeeding is not possible, the choice of the milk is made among hundreds of formulas for infants. They are regulated by a European directive. The healthcare professionals have to recommend as often as possible an infant formula: low protein content, predominance of whey proteins, enrichment with long chain fatty acids, lactose, addition of pre- or probiotics. The formulas for specific indications will be recommended in case of particular situations after verification that the complaints (constipation, regurgitations, stomach pains) cannot be corrected by simple dietary measures (increasing of the intakes of meals with a concomitant reduction of the volume of the meals). The food diversification is recommended between 17 and 26 weeks according to the neuromuscular capacities of the infant. These meals must be presented with a spoon to assure a sufficient nutritional intake. In Belgium, the use is to begin with fruits. One should avoid adding biscuits or sugar. The meal of vegetables will be introduced a little later. It should consist of starchy foods, vegetables with some fat to which the meat will be added. Numerous foods (biscuits, croissants and similar products, chips) should never be part of the ordinary menu, but should be reserved for particular occasions. The education of the children should begin from this age on.

Objectives: Previous studies of infant formulas supplemented with oligosaccharides reported mixed results regarding the impact on intestinal microbial populations. The objective of this study was to examine the effect of supplementation of an infant formula with fructo-oligosaccharides (FOS) on select groups of intestinal bacteria in term infants., Methods: Four groups of infants were enrolled and fed human milk, a commercially available milk-based infant formula, or infant formula supplemented with 2.0 or 3.0 g/L FOS. Dietary intake, stool, and tolerance events were recorded. Fresh stool samples were collected approximately 27 days after feeding the diets (approximately 32 days after birth). Total bacteria, Bacteroides (as commensal bacteria), Bifidobacterium and Lactobacillus, and Clostridium difficile and Escherichia coli were quantified using respective specific real-time PCR assays., Results: The formula feeding groups did not differ in stool consistency and stool frequency or frequency of spit-up or vomit during the entire study. The formula-fed infants tended to have more total bacteria in their stool samples than the human milk-fed infants. The formula-fed infants harbored a greater abundance of C difficile and E coli than the human milk-fed infants, but had a similar abundance of Bacteroides, Bifidobacterium, and Lactobacillus. The FOS supplementation at either dose did not significantly increase the bifidobacterial or lactobacilli populations, or decrease the populations of C difficile, E coli, or Bacteroides., Conclusions: The milk-based formula used in this study supported bifidobacterial and lactobacilli populations comparable with the human milk group; however, this formula did not suppress E coli or C difficile as effectively as human milk.

Objective: To identify the effects of infant formula on the reproductive development of Spraque-Dawley rats., Methods: A two-generation reproductive test was carried out. Forty 4 week-old SD rats were divided into two groups randomly by body weight and maintained on diet containing a kind of infant formula or an adjusted basal feeds. The body weight, dietary intake, hormone level, function of reproductive organs, and the development status of the P generation rats and F1 generation rats were measured., Results: No significant growth-promoting effect was observed in the infant formula group; and no impairment on reproductive organ development or development status in the P generation and F1 generation rats was caused by the infant formula. The body weight at the 14th day of gestation and at the 0th and 4th day of lactation in infant formula group was significantly lower than that in control group (P < 0.05). The level of prolactin was significantly lower in the infant formula group. The AGD of F2a female rats was significantly shorter in the infant formula group., Conclusion: There was few effect of the infant formula on the reproductive development of SD rats, further study is required to determine the effects of infant formula on the body weight change during gestation period and lactation period, AGD and prolactin level.

Diet in early infancy has an impact on early growth and the formation of flavour preferences, as well as on later life health outcomes. Although breast milk is the preferred source of nutrition during infancy, more than half of American infants receive infant formula by the age of 4 months. As a group, formula-fed infants weigh more by the age of one year and have a greater risk for later obesity than breastfed infants. However, a recent randomized study found that, when compared to breastfed infants, infants fed an extensively hydrolysed protein formula (ePHF) had more normative weight gain velocity than infants fed cow's milk formula (CMF). Therefore, grouping all formula-fed infants together with respect to certain health outcomes such as obesity may not be appropriate. Scientific evidence also suggests that there are sensitive periods for flavour learning. Infants become familiar with and learn to accept the flavours they experience through their mother's amniotic fluid and breast milk as well as formula. These early experiences influence flavour preferences of children that may affect food choices and therefore later life health. Further research on the influence of early diet on growth, flavour preferences, and food choices is imperative.

Healthy 9- to 48-month-old children (n = 133) were randomized to receive a cow's-milk-based follow-on formula (control) or the same formula with polydextrose and galactooligosaccharides (PDX/GOS) for 108 days. Pediatricians assessed diarrheal disease, stool pattern, acute respiratory infection, systemic antibiotic use, and growth. The 2 groups had similar weight-for-length/height z score and similar odds of having diarrheal disease, acute respiratory infection, and systemic antibiotic use; however, PDX/GOS had greater odds of increased defecation than control (P ≤ 0.01). Addition of PDX and GOS to a follow-on formula was well tolerated and induced a pattern of more frequent and softer stools in toddlers.

Background/objectives: Preterm infants are at risk for low vitamin D but documentation on late-preterm infants is sparse. This prospective study monitored longitudinally vitamin D and parathormone (PTH) levels in late-preterm formula fed infants during the first year of life, taking into consideration in utero and postnatal growth, and season and diet., Subjects/methods: The study population comprised 128 infants of gestational age (GA) 32-36 weeks, of which 102 were appropriate (AGA) and the remaining 26 were small for GA (SGA). Serum levels of vitamin D (25(OH)D), PTH calcium, phosphate (P) and alkaline phosphate were estimated at 2 and 6 weeks, and at 3, 6, 9 and 12 months of age., Results: The 25(OH)D levels were relatively low at 2 and 6 weeks in both AGA and SGA infants (21±11, 20±7 ng/ml and 25±16, 23±8 ng/ml, respectively), but increased at 6 months (45±14, 47±10 ng/ml) and remained stable thereafter. SGA infants had lower 25(OH)D levels at 9 and 12 months (AGA 45±14, 47±18 ng/ml vs SGA 38±13, 37±13 ng/ml, P<0.05). Deficiency of 25(OH)D (<20 ng/ml) was found in 18.5% of measurements in 92 (72%) infants, and its insufficiency (20-32 ng/ml) was found in 29.2% of measurements in 99 (77.3%) infants. Most measurements with vitamin D <32 ng/ml were observed at the first three study points, where PTH showed an inverse association with 25(OH)D, reaching a plateau thereafter., Conclusions: Late-preterm, formula fed infants may have suboptimal vitamin D levels and elevated PTH, especially, during the first 3 months. Those born SGA may have lower vitamin D levels up to the end of the first year of life.

Melamine is a nitrogen-rich industrial chemical which is occasionally used to increase the apparent protein content of different products destined for human and animal consumption. In this work, a liquid chromatographic procedure that uses micellar mobile phases of sodium dodecyl sulfate (SDS) buffered at pH 3, a C18 column and UV detection is reported for the determination of melamine in dietetic supplements. Samples were reconstituted with a SDS solution and were directly injected, thus avoiding long extraction and experimental procedures. Melamine was eluted in less than 10 min with no interference by other compounds of the matrices. The optimum mobile phase composition was taken by a chemometrical approach that considers the retention factor, efficiency and peak shape. Validation was performed following the indications of the European Commission (Decision 2002/657/EC). The following parameters were considered: linearity (0.02-100 μg mL(-1); R(2) = 0.9996), intra- and inter-day precisions (<12.4%), accuracy (90.0-101.3%), and robustness (less than 9.8% and 5.1%, for retention time and peak area, respectively). The limits of detection and quantification were 9 and 20 ng mL(-1), respectively. Recoveries for several spiked samples were in the 85.8-114.3% range. These results indicate that the proposed methodology is useful for routine analysis of control quality of infant formula and adult dietetic supplements., (This journal is © The Royal Society of Chemistry 2012)

Purpose: To investigate the effect of different milk formulas on dental plaque pH., Materials and Methods: Six commercial infant milk formulas were selected, with 10% sucrose solution as the positive and deionised water as the negative control, and tested among ten children aged 7-10 years. The plaque pH changes were recorded by using a combination electrode., Results: Mouth rinsing with all infant formulas significantly reduced the plaque pH (Tukey's multiple comparison test, P < 0.05) to levels below the pre-rinse pH value for sucrose solution and also below the pH obtained after rinsing with water. Each milk formula had a significant but variable buffering effect or tendency to decrease the pH. The formula with the least buffering effect was Nestogen (9.21%) followed by Nan (11.92%), and the highest buffering effect was shown by Lactodex (20.13%). The pH drop ranged from 0.72 for Farex to 0.98 for Nan., Conclusion: The results of this study underscore the need for parents and clinicians to be fully aware of the potential harm of various infant formulas and their major role in the etiology of ECC. These findings may help in creating a new generation of foods which, if not 'friendly to teeth', may be thought of as 'friendlier' than their predecessors.

In the U.S. formula feeding remains more popular than breast-feeding. In the current study, neonatal piglets were breast fed and compared with those fed commercially available milk-based formula (milk) or soy-based formula (soy) from postnatal day 2 (PND2) until death at PND21 (the usual age of weaning). Liver weights were greater in formula-fed piglets (P<0.05) than in breast-fed piglets (P<0.05). Affymetrix array analysis revealed significant differences in hepatic gene expression signatures between piglets fed breast milk or formula, as well as between piglets fed milk or soy. In males, expression of 346 hepatic genes differed between formula-fed and breast-fed piglets, and soy-fed differed from milk-fed piglets in 277 genes. Furthermore, gene expression profiles of males differed from females, even when the same diet was consumed. Serum cholesterol was lower in piglets fed formula relative to breast-fed piglets (P<0.05), and this was associated with elevations in mRNA encoding cholesterol 7α-hydroxylase (CYP7A1). Consistent with the human literature, breast-fed piglets had lower hepatic iron accumulation than formula-fed piglets. Hepcidin, a major regulator of hepatic iron trafficking, was elevated in piglets fed formula relative to breast-fed piglets (P<0.05). Female piglets fed soy formula had increased expression of CYP3A enzymes (P<0.05), and soy formula feeding decreased expression of several hepatic genes considered estrogen inducible. These data suggest that: 1) gene expression profiles in neonates differ significantly depending on the diet consumed, 2) hepatic iron storage and cholesterol metabolism clearly differ between breast and formula feeding in piglets, 3) there is no evidence that soy is estrogenic in neonatal pig liver.

Objective: To test the hypothesis that long-chain polyunsaturated fatty acid (LCPUFA) supplementation in infancy would improve cognition into later childhood (after 9 years) at both general and specific levels., Methods: A comprehensive cognitive battery was completed by 107 formerly preterm infants (mean age: 128 months). As infants, they had been assigned randomly to receive LCPUFA-supplemented (N = 50) or control (N = 57) formula, between birth and 9 months; the docosahexaenoic acid level (DHA) in the supplemented formulas was 0.5%. In addition to randomized comparisons, we planned supplementary analyses to examine the effects of both gender and feeding group (those receiving some maternal breast milk versus those receiving none)., Results: There were no significant differences between randomized diet groups on any cognitive measure. There was significant interaction between gender and supplementation; girls only showed beneficial effects of LCPUFAs on literacy. Significant interaction also occurred between feeding group and supplementation; increases of 0.7 SD in verbal IQ, full-scale IQ, and memory scores were found for the LCPUFA group, but only for infants who received only formula and no maternal breast milk., Conclusions: The results of this post-9-year cognitive follow-up study in a randomized trial of LCPUFA-supplemented formula for preterm infants suggest no overall group effects but indicate that gender-specific and diet-specific effects may exist. The data provide some evidence that LCPUFAs are a key factor in the cognitive benefits of breast milk. Caution is advised in data interpretation because of the small groups used.

Necrotizing enterocolitis (NEC) in preterm infants develops very rapidly from a mild intolerance to enteral feeding into intestinal mucosal hemorrhage, inflammation, and necrosis. We hypothesized that immediate feeding-induced gut responses precede later clinical NEC symptoms in preterm pigs. Fifty-six preterm pigs were fed total parenteral nutrition (TPN) for 48 h followed by enteral feeding for 0, 8, 17, or 34 h with either colostrum (Colos, n = 20) or formula (Form, n = 31). Macroscopic NEC lesions were detected in Form pigs throughout the enteral feeding period (20/31, 65%), whereas most Colos pigs remained protected (1/20, 5%). Just 8 h of formula feeding induced histopathological lesions, as evidenced by capillary stasis and necrosis, epithelial degeneration, edema, and mucosal hemorrhage. These immediate formula-induced changes were paralleled by decreased digestive enzyme activities (lactase and dipeptidylpeptidase IV), increased nutrient fermentation, and altered expression of innate immune defense genes such as interleukins (IL-1α, IL-6, IL-18), nitric oxide synthetase, tight junction proteins (claudins), Toll-like receptors (TLR-4), and TNF-α. In contrast, the first hours of colostrum feeding induced no histopathological lesions, increased maltase activity, and induced changes in gene expressions related to tissue development. Total bacterial density was high after 2 days of parenteral feeding and was not significantly affected by diet (colostrum, formula) or length of enteral feeding (8-34 h), except that a few bacterial groups (Clostridium, Enterococcus, Streptococcus species) increased with time. We conclude that a switch from parenteral to enteral nutrition rapidly induces diet-dependent histopathological, functional, and proinflammatory insults to the immature intestine. Great care is required when introducing enteral feeds to TPN-fed preterm infants, particularly when using formula, because early feeding-induced insults may predispose to NEC lesions that are difficult to revert by later dietary or medical interventions.

Surfactant proteins A (SP-A) and SP-B are critical in the ability of pulmonary surfactant to reduce alveolar surface tension and provide innate immunity. Aspiration of infant milk formula can lead to lung dysfunction, but direct effects of aspirated formula on surfactant protein expression in pulmonary cells have not been described. The hypothesis that infant formula alters surfactant protein homeostasis was tested in vitro by assessing surfactant protein gene expression in cultured pulmonary epithelial cell lines expressing SP-A and SP-B that were transiently exposed (6 hr) to infant formula. Steady-state levels of SP-A protein and mRNA and SP-B mRNA in human bronchiolar (NCI-H441) and mouse alveolar (MLE15) epithelial cells were reduced in a dose-dependent manner 18 hr after exposure to infant formula. SP-A mRNA levels remained reduced 42 hr after exposure, but SP-B mRNA levels increased 10-fold. Neither soy formula nor non-fat dry milk affected steady-state SP-A and SP-B mRNA levels; suggesting a role of a component of infant formula derived from cow milk. These results indicate that infant formula has a direct, dose-dependent effect to reduce surfactant protein gene expression. Ultimately, milk aspiration may potentially result in a reduced capacity of the lung to defend against environmental insults., (Copyright © 2011 Wiley-Liss, Inc.)

Rationale: The role of infant formula aspiration in lung injury has not been studied extensively. We evaluated the effects of a single infant formula aspiration into the lungs of mice and the effect of infant formula exposure on cell lines representing murine alveolar macrophages and type II epithelial cells., Objectives: To study the effects of exposure to infant formula on cell count histology and cytokine levels in an in vivo and in vitro model of aspiration., Methods: In vivo: Juvenile mice received 2.5 µl/g of 50% infant formula intranasally. Bronchoalveolar lavage samples were collected at 1, 2, and 7 days after aspiration and evaluated for cell count and differential. In vitro: RAW 264.7 and MLE-15 cells were exposed to 1% infant formula for 6 hr. Extracellular levels of IL-6, TNF-α, MIP-2, and KC were measured in lavage fluid and cell media using ELISA assays., Results: In vivo: An increase in neutrophils, IL-6 and KC levels were noted 24 hr after infant formula exposure. In vitro: An increase in TNF-α levels from RAW 264.7 and MIP-2 and KC levels from MLE-15 cells was noted after infant formula exposure., Conclusions: A single aspiration of infant formula into the lungs leads to an acute inflammatory response involving both lung macrophages and epithelial cells., (Copyright © 2011 Wiley-Liss, Inc.)

The hypothesis that nutrition during critical windows in fetal and early life can program long-term health is intriguing and has a potentially strong implication for public health and pediatric nutritional practice. Specifically, it has been hypothesized that there are critical periods in the differentiation and maturation of the central nervous system during which environmental and nutritional factors can produce long-term structural and/or functional changes. Many studies have focused on the relationship between nutrition during early life and long-term neurodevelopmental outcome, leading to contrasting results: in fact, although experimental data in animals and short-term follow-up studies indicate a possible relationship between nutrition during early life and neurodevelopment, the results of long-term follow-up studies are more controversial and less convincing., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Our study aimed at investigating the impact of the level of protein in milk formula on intestinal structure, barrier function, and its nervous regulation in normal and LBW neonates using a porcine model. Normal birth weight (NBW) or LBW piglets were fed from d7 to d28 of age either with a high protein (HP) or with an adequate protein (AP) formula or stayed with their mother [mother fed (MF)]. The proximal jejunum and distal ileum were sampled at d28 for morphometry analysis and ex vivo permeability measurement in Ussing chambers. Formula feeding induced a trophic effect on the jejunum and ileum of both NBW and LBW piglets, which exhibited longer villi than MF animals, irrespective of the type of formula. In NBW piglets, intestinal permeability was not altered by formula feeding. On the contrary, LBW piglets fed with HP formula, but not AP, exhibited a greater ileal permeability than MF piglets. Feeding the HP formula also disturbed jejunal and ileal regulation of permeability by acetylcholine and vasoactive intestinal peptide (VIP) in LBW compared with MF LBW piglets. In conclusion, the level of protein in formulas did not modify intestinal structure and function in NBW individuals but dramatically modified intestinal barrier function physiology in LBW individuals.

Objective: Infants with a documented hereditary risk of atopy (i.e., an affected parent and/or sibling) who cannot be breastfed exclusively are recommended to receive a formula with confirmed reduced allergenicity, i.e., a partially or extensively hydrolyzed formula (pHF and eHF, respectively), as a means of preventing allergic reactions. The efficacy of each hydrolyzed formula for the prevention of allergic diseases should be established separately, as factors such as the protein source, hydrolysis method and degree of hydrolysis that often depend on the manufacturer contribute to differences among hydrolysates. The aim was to systematically review data on the efficacy of a partially hydrolyzed 100% whey formula (pHF) in reducing the risk of allergy in healthy infants at high risk for allergy., Methods: The Cochrane Library, MEDLINE, EMBASE, and CINAHL databases were searched in September 2009 (from inception to September 2009) for randomized and quasi-randomized controlled trials (RCTs); additional references were obtained from reviewed articles. The company that manufactures the pHF used was contacted for unpublished data., Results: The search yielded 84 citations. Fifteen RCTs were included, some of which had potential methodological limitations such as unclear or inadequate allocation concealment, no intention-to-treat analysis, and no true blinding. For primary outcomes, i.e., all allergic diseases and atopic eczema/atopic dermatitis, use of the pHF compared with standard formula (SF) was associated with reduced risks (incidence, cumulative incidence, period prevalence) that were statistically significant for most, albeit not all, time points. Comparison of groups who received the pHF versus extensively hydrolyzed (eH) whey formula revealed no significant differences in outcomes except for reductions in the cumulative incidences of all allergic diseases at 0 to 36 months of age. Comparison of groups who received the pHF versus eH casein formula revealed no significant difference in outcomes between groups., Conclusions: The use of the pHF compared to SF is effective in allergy prevention in children at high risk for allergy at most time points. These results should be interpreted with caution due to a lack of methodological rigor in many trials. Reassuringly, the strongest evidence comes from a well-designed and conducted, independently funded RCT.

Background and Objectives: Postdischarge formulas with extra energy and protein improve short-term growth but may also influence long-term body composition in an unwanted manner. Energy- and protein-enriched formulas with an increased protein-to-energy ratio improves gain of lean mass. The objective of the study was to investigate whether feeding a nutrient-enriched formula without extra energy after term, usually 3 to 4 weeks after discharge, would influence growth and body composition in infancy., Methods: In this randomized controlled trial preterm infants were fed fortified human milk or preterm formula until term. At term, 102 infants were randomized to a nutrient-enriched formula without extra energy or standard formula until 6 months corrected age. Twenty-six infants received unfortified human milk after term. At term and 6 months corrected age, anthropometry and a dual-energy x-ray absorptiometry (DEXA) scan were performed. Lean and fat mass (FM) were corrected for height., Results: There were no differences in growth or body size between the feeding groups. Infants fed the enriched formula gained less FM and had lower FM corrected for body size at 6 months corrected age than infants fed standard formula. Infants fed human milk had lower lean mass and higher FM corrected for body size at 6 months corrected age than formula-fed infants., Conclusions: Feeding nutrient-enriched formula without extra energy after term does not change quantity of growth but does influence type of weight gain and body composition of preterm infants. Infants fed the nutrient-enriched formula had lower FM corrected for body size at 6 months corrected age than infants fed standard formula or human milk.

Although the American Academy of Pediatrics and the American Academy of Family Physicians recommend breast milk for optimal infant nutrition, many parents still choose formula as an acceptable alternative. The wide variety of available formulas is confusing to parents and physicians, but formulas can be classified according to three basic criteria: caloric density, carbohydrate source, and protein composition. Most infants require a term formula with iron. There is insufficient evidence to recommend supplementation with docosahexaenoic acid or arachidonic acid. Soy formulas are indicated for congenital lactase deficiency and galactosemia, but are not recommended for colic because of insufficient evidence of benefit. Hypoallergenic formulas with extensively hydrolyzed protein are effective for the treatment of milk protein allergy and the prevention of atopic disease in high-risk infants. Antireflux formulas decrease emesis and regurgitation, but have not been shown to affect growth or development. Most infants with reflux require no treatment. Family physicians can use these guidelines to counsel parents about infant formula, countering consumer advertising that is not evidence-based.

Context: Currently, thickened feeds are increasingly being used to treat infants with gastroesophageal reflux, driven in large part by the baby food industry. Previous meta-analyses have shown that although thickened formulas do not seem to reduce measurable reflux, they may reduce vomiting. However, because data are limited, there is still uncertainty regarding the use of thickening agents., Objective: Our goal was to systematically evaluate and update data from randomized, controlled trials on the efficacy and safety of thickened feeds for the treatment of gastroesophageal reflux in healthy infants., Methods: The Cochrane Library, Medline, Embase, and CINAHL databases and proceedings of the European and North American pediatric gastroenterology conferences (from 2000) were searched in May 2008; additional references were obtained from reviewed articles. Only randomized, controlled trials that evaluated thickened feeds used in infants for at least several days for the treatment of gastroesophageal reflux were considered for inclusion. Three reviewers independently performed data extraction by using standard data-extraction forms. Discrepancies between reviewers were resolved by discussion between all authors. Only the consensus data were entered., Results: Fourteen randomized, controlled trials with a parallel or crossover design, some with methodologic limitations, were included. Use of thickened formulas compared with standard formula significantly increased the percentage of infants with no regurgitation, slightly reduced the number of episodes of regurgitation and vomiting per day (assessed jointly or separately), and increased weight gain per day; it had no effect on the reflux index, number of acid gastroesophageal reflux episodes per hour, or number of reflux episodes lasting >5 minutes but significantly reduced the duration of the longest reflux episode of pH<4. No definitive data showed that one particular thickening agent is more effective than another. No serious adverse effects were noted., Conclusions: This meta-analysis shows that thickened food is only moderately effective in treating gastroesophageal reflux in healthy infants.

According to recent epidemiologic evidence, introducing solids while infants are still breastfed, and in any case not before the fourth month of life, could have positive impact on immune-related chronic disorders such as Type 1 Diabetes and coeliac disease.

Background: Regurgitation is frequent in infants. We evaluated changes in regurgitation among patient groups fed standard formula, standard formula subsequently thickened with cereal, or formula manufactured with bean gum as a thickening agent., Patients and Methods: A prospective, blinded, randomised 1-month intervention trial evaluating the efficacy of parental reassurance of the regurgitating child in combination with 3 formula interventions--standard infant formula (group A); 5 g of rice cereal added to 100 mL standard formula (group B); and formula manufactured with bean gum as a thickening agent (group C)--was performed in 60 infants presenting with more than 4 episodes of regurgitation and/or vomiting per day during the week before inclusion. Formula intake, infant comfort, stool aspects, and weight gain were evaluated. All of the infants and data recorded by parents in a diary were evaluated weekly by a blinded health care professional., Results: At baseline, groups A, B, and C were similar for all of the parameters. After the 1-month intervention, regurgitation/vomiting decreased significantly in all 3 groups (P < 0.0005). Although the decrease was largest in group C (-4.2 +/- 2.1 episodes/day), the incidence did not differ significantly with groups A or B. At no evaluation interval was there a difference in volume of formula intake, infant comfort, stool frequency, or aspect. After 1 month, weight gain was significantly greater in group C compared with group A (19.9% vs 16.4%; P < 0.001)., Conclusions: Thickening of formula decreases regurgitation, but not significantly. Parental reassurance remains the cornerstone of the treatment of infant regurgitation.

In recent decades, there has been a dramatic increase in the incidence of obesity in all age groups of the population in the USA. In addition to genetics and life style changes, the important role of metabolic programming effects in the etiology of the obesity epidemic is being increasingly recognized. Although the role of a compromised intrauterine environment in fetal metabolic programming is well documented to contribute to the development of adult-onset diseases, vulnerability in the immediate postnatal period to similar conditions has also been shown. Metabolic programming effects induced by altered nutritional experiences in the immediate postnatal period can give rise to long-term consequences in the context of the current obesity epidemic.

Adiponectin has potent insulin-sensitizing effects, improves lipid metabolism, and potentially protects against the development of metabolic syndrome. Thus, increasing adiponectin levels in preterm infants at risk for developing metabolic syndrome may be of special interest. The aim of this study was to examine the effects of dietary long-chain polyunsaturated fatty acids (LCPUFA) on serum adiponectin and lipid concentrations in preterm infants. Adiponectin and lipid levels of 60 healthy preterm infants [gestational age 32.7 (1.9) wk] randomly assigned to be fed either 1) a formula containing LCPUFA [arachidonic and docosahexanoic] (+LCPUFA group) or 2) the same formula without LCPUFA (-LCPUFA/control group), were determined at mean (SD) 33.8 (11.7) d. Adiponectin and HDL-C concentrations were significantly higher in the +LCPUFA group than in controls (p = 0.002 and p = 0.01, respectively); whereas, triglyceride levels were lower (p = 0.06). Adiponectin correlated positively with HDL-C levels and negatively with triglyceride levels in the +LCPUFA group but not in the controls. In conclusion, circulating adiponectin concentrations were higher in preterm infants fed a formula containing LCPUFA than infants fed an LCPUFA-free formula and they correlated with lipidemic profile.

Background: A study was undertaken to examine factors that might influence lung function during infancy and to test the hypothesis that change in weight during infancy is negatively associated with change in lung function., Methods: Weight, length and maximal flow at functional residual capacity (V'maxFRC) were measured at ages 1 and 12 months. V'maxFRC was adjusted for length. Asthma symptoms and age at introduction of formula feeds were identified from questionnaires. Groups were dichotomised by V'maxFRC at 1 month and change in V'maxFRC., Results: 154 infants were assessed at ages 1 and 12 months. The change in V'maxFRC was inversely associated with change in weight (r = -0.18, r2 = 0.13, p<0.001). The group with lower V'maxFRC at 1 month and reduced change in V'maxFRC over infancy had the greatest weight gain (p = 0.003) and increased risk for asthma symptoms by 3 years (p = 0.017) but not afterwards. Exclusive breast feeding to 6 months was associated with a mean reduction in weight gain at age 12 months in comparison with earlier introduction of formula milk (mean difference 0.65 kg, p = 0.001), and was also associated with reduced asthma symptoms at 3 years (odds ratio 0.44, p = 0.043) but not at 6 or 11 years of age., Conclusions: Weight gain in infancy is inversely associated with change in lung function during infancy. Postnatal weight gain may be indirectly associated with early transient asthma symptoms via an influence on lung growth during infancy, and this is potentially modifiable by breast feeding. These associations could be relevant to the clinically recognised syndrome of the "fat happy wheezer".

Objective(s): Advantages of prethickened formulas (AR) with regards to esophageal pH and gastric emptying were investigated in this study as compared with a regular formula (R)., Study Design: Seventy-four healthy infants, <6 months old, with gastroesophageal reflux were enrolled into the study. All infants underwent 24-hour esophageal pH monitoring while receiving R and AR, alternately. Electrogastrography was measured before and after feeding each study formula. Thereafter, the infants were randomly assigned to receive either R or AR for 1 month. Episodes of regurgitation, vomiting, coughing, crying, and bowel movements were recorded on a weekly interval., Results: Reflux index (RI) of AR-fed infants were lower (5.64%) than the R-fed infants (7.77%) showing a significant difference (P<0.01) between the 2 groups, favoring AR. Eighty-seven percent of infants improved their RI while receiving the AR formula. Electrogastrography variables were not significantly different between the 2 study groups. A significant decrease (P<0.01) in the daily episodes of regurgitation and vomiting was observed in the AR-fed infants. No adverse events were reported during the study., Conclusions: Prethickened infant formula was effective in reducing clinical symptoms of uncomplicated gastroesophageal reflux and reducing RI. Prethickened formulas do not alter gastric emptying time and was very well tolerated.