Milk Protein-based Formula Research Articles

Infant formula with added Lacticaseibacillus rhamnosus GG supported adequate growth and was well tolerated in healthy term infants: a randomized controlled trial.

Lacticaseibacillus rhamnosus GG (LGG) is a well-studied probiotic with a history of safe use. In this double-blind, prospective study, growth and tolerance were evaluated in healthy term infants randomized to: marketed, routine intact cow's milk protein-based formula (Control, n = 172) or a similar investigational formula with added LGG (INV-LGG, n = 179; 106 CFU LGG®/g powder) from 14 to 120 days of age. Anthropometrics, stool characteristics, fussiness, and gassiness were evaluated through Day 120. Medically confirmed adverse events were recorded throughout the study period. The primary outcome was rate of weight gain from Day 14-120. Of 351 infants enrolled, 275 completed (Control, n = 131; INV-LGG, n = 144). No significant group differences in rate of weight gain from Day 14-120 were detected. Study formula acceptance and tolerance was good with no significant differences in study discontinuation due to study formula or parent-reported gassiness, stool frequency, or stool consistency; however mean fussiness relative to normal was significantly lower for INV-LGG vs Control at Days 60 and 90. In healthy term infants, a routine intact cow's milk protein-based formula with added LGG supported adequate growth and was well tolerated. Further studies are needed to evaluate potential benefits for fussiness and efficacy outcomes. Clinicaltrials.gov, identifier (NCT01897922).

Growth and gut comfort of healthy term infants exclusively fed with a partially hydrolysed protein-based infant formula: a randomized controlled double-blind trial.

This study aimed to investigate growth and gut comfort of healthy infants fed with a partially hydrolysed cow's milk protein-based infant formula (pHF) compared to a standard intact cow's milk protein-based formula (IPF). A double-blind, multi-center, randomized, controlled trial was performed. Healthy full-term, exclusively formula-fed infants (n = 345), aged ≤28 days were allocated to consume either a pHF (n = 173) or an IPF (n = 172) until the age of 17 weeks. The primary outcome was equivalence of weight gain (g/d) until the age of 17 weeks. The secondary outcomes were equivalence of other growth parameters, i.e., infants' weight, length, head circumference, body mass index (BMI) and anthropometric Z-scores, while tertiary outcomes were gut comfort, formula intake, and adverse events (AEs). Overall, 288 infants completed the study (pHF group: 138, IPF group: 150). No differences were observed between the two groups in weight gain (g/d) during the three-months intervention [p = 0.915 for the Per Protocol (PP) population]. The 90% CI was [-1.252 to 1.100] being within the pre-defined equivalence margin of ±3.0 g/d. Similar findings were observed in the Full Analysis Set (FAS) and the sensitivity analysis. Regarding the secondary outcomes, no differences over the intervention period were shown between the two groups in both the PP and FAS analysis sets. Average Z-scores were in the normal range based on World Health Organization (WHO) growth standards for both groups at all time points in both analysis sets. Stool consistency, amount, and colour were different in the two groups. No differences were observed in gut comfort, stool frequency, and formula intake, between the two groups. In total 14 AEs and 22 serious adverse events (SAEs) were reported of which 15 (12%) and 1 (5%) were considered as (possibly) related to the study product, respectively. The study demonstrates that the consumption of pHF results in adequate infant growth, equivalent to that of infants consuming IPF. Furthermore, the overall gut comfort was comparable between the two groups. Therefore, it can be concluded that the pHF is safe for and well tolerated by healthy infants. https://clinicaltrials.gov/study/NCT05757323?id=NCT05757323&rank=1, identifier (NCT05757323).

Tolerability of partially and extensively hydrolysed milk formulas in children with cow's milk allergy.

The safety and tolerability of hydrolysed cow's milk protein-based formulas, particularly partially hydrolysed formulas (pHFs), in children with cow's milk allergy (CMA) remain poorly understood. We evaluated the tolerability of hydrolysed cow's milk-based formulas in children with CMA. A three-period double-blind crossover evaluation compared the allergic tolerance against three dietary cow's milk-based formulas: extensively hydrolysed cow's milk formula (eHF), pHF, and regular cow's milk formula (rCMF). The primary outcome was the rate of tolerance against a maximum of 20.0 mL of formula. Controlled food challenges were performed in 25 children (18 boys; 7 girls) with a median age of 4.25 years (range: 1-9 years) diagnosed with CMA. The median cow's milk-specific immunoglobulin E level was 31.9 UA/mL (range: 1.16-735 UA/mL). The tolerance rate ratios for rCMF were lower than those for pHF (2 vs 16; p<0.01) and eHF (2 vs 22; p<0.01). The allergic symptom scores induced by intake of pHF and eHF were significantly lower than those of rCMF (p=0.01 and p<0.01, respectively), and the pHF and eHF scores were not significantly different. Compared to rCMF, the partially and extensively hydrolysed whey and casein formulas evaluated in this study were better tolerated and therefore safer for children with CMA. Although further confirmation from additional centres is needed, our findings suggest the use of pHF in patients with mild CMA. Some children with CMA react to hydrolysed formulas; therefore, food challenge tests in these children should be undertaken with caution.

Oral Immunotherapy Using Partially Hydrolyzed Formula for Cow’s Milk Protein Allergy: A Randomized, Controlled Trial

Background: Partially hydrolyzed cow’s milk protein-based formula (pHF) possesses low allergenicity. Here, we investigate the safety and efficacy of oral immunotherapy using pHF for children with cow’s milk protein allergy (CMPA). Objectives: A randomized, double-blind, controlled single-center trial was conducted to evaluate the efficacy and safety of pHF oral immunotherapy in children with CMPA. Methods: Participants were randomized into double-blind pHF-pHF and extensively hydrolyzed cow’s milk protein-based formula (eHF)-pHF groups. During this phase, the pHF-pHF group received pHF and the eHF-pHF group received eHF. During the open phase, all participants received pHF. The primary end point was a change in thresholds between baseline and the end of the first phase. Secondary end points were changes in thresholds between baseline and the end of the second phase, and casein-specific immunoglobulin (Ig)E, IgG₄, and basophil activation. Results: Twenty-five children, aged 1–9 years, were randomized into pHF-pHF and eHF-pHF groups. The threshold between baseline and the end of the first phase was significantly elevated in the pHF-pHF group (p = 0.048), but not in the eHF-pHF group. The threshold between other phases did not change significantly in either group. There were significant decreases in casein-specific IgE antibody levels between baseline and the second phase in the eHF-pHF group (p = 0.014). No participants suffered systemic allergic reactions requiring adrenaline or systemic corticosteroids after receiving the formulas. Conclusions: The results of this trial suggest that, in children with CMPA, tolerance to cow’s milk might be safely enhanced by intake of pHF, relative to that of eHF.

Milk protein-based formulas containing different oils affect fatty acids balance in term infants: A randomized blinded crossover clinical trial

BackgroundPalm olein is used in infant formula fat blends in order to match the fatty acid profile of human milk. While the effects on fatty acid balance have been evaluated, the use of palm olein in combination with palm kernel oil and supplementation with docosahexaenoic acid (DHA) and arachidonic acid (ARA) has not been similarly assessed in infants. This study evaluated the effects of infant formulas containing different fat compositions on the balance of fat, fatty acids, and calcium.MethodsIn this randomized, crossover, double-blinded study, 33 healthy term infants (68–159 ± 3 days of age at enrollment) were fed two formulas for 14 days in a tolerance period, followed by a 4-day metabolic balance period in 17 of the male subjects. The study compared two commercially available milk-based powdered formulas in Brazil; the PALM formula contained palm olein (44%), kernel palm oil (21.7%), and canola oil (18.5%) as the predominant fats, whereas the NoPALM formula contained other fat sources.ResultsFat absorption (%) was greater for NoPALM versus PALM-fed infants (96.55 and 95.50%, respectively; p = 0.023). The absorption percentage of palmitic acid (C16:0) did not differ significantly between formulas (p > 0.05), but this acid was excreted at significantly higher concentrations in the PALM (29.42 mg/kg/day) than in the NoPALM (12.28 mg/kg/day) formula groups. DHA and ARA absorption percentages were also higher in NoPALM-fed infants. Calcium absorption was higher in NoPALM-fed infants (58.00%) compared to those fed PALM (40.90%), but the difference was not significant (p = 0.104) when calcium intake was used as a covariate. However, calcium retention was higher in NoPALM-fed infants compared to that in PALM-fed infants with or without calcium intake as a covariate. Adverse events did not differ between groups (p > 0.05).ConclusionsThe absorption of essential fatty acids was similar for both formulas; however, long-chain polyunsaturated fatty acids (DHA and ARA) were better absorbed from the NoPALM formula. Fat absorption and calcium retention were lower in term infants fed the PALM-based formula.Clinical trial registrationClinicaltrial.gov # NCT00941564.

Assessment of the effect of methionine supplementation and inclusion of hydrolyzed wheat protein in milk protein-based milk replacers on the performance of intensively fed Holstein calves

The objectives of this study were to compare 2 milk replacers containing only milk proteins with or without supplemental Met, and to compare a milk replacer containing hydrolyzed wheat protein at 4.5% of dry matter (DM) and supplemental Lys and Met against the 2 all-milk-protein formulas, by assessing their effect on the growth performance, efficiency, and plasma urea nitrogen of pre-weaning Holstein calves. Thus, 57 Holstein calves were allotted to the following 3 treatments: (1) a skim milk plus whey protein concentrate-based milk replacer (SMWP) containing about 2.6% Lys and 0.6% Met on a DM basis; (2) SMWP + M based on skim milk and whey proteins, containing about 2.6% Lys, and supplemental Met to reach 0.9% on a DM basis; and (3) a skim milk plus whey protein concentrate plus 4.5% of the DM as hydrolyzed wheat protein based milk replacer (HWP + LM) where the wheat protein replaced 50% of the whey protein concentrate, and also contained supplemental Lys and Met to match the profile of SMWP + M (i.e., Lys 2.6 and Met 0.9% on DM basis). No difference in any of the responses was observed by supplementing the milk protein based formula with Met or when hydrolyzed wheat protein was added to the formula. Results indicate that (1) a milk replacer based on skim milk protein and whey protein with a Lys concentration of ~2.6% does not benefit from Met supplementation, and (2) milk replacer containing 4.5% of the DM as hydrolyzed wheat protein and supplemented with Lys and Met can support the same growth performance as milk protein-based formulas.

Predictors of childhood food allergy

Background Food allergy is a relatively common pediatric problem, affecting 5-8% of young children. Its occurrence is strongly associated with other atopies, and it is a main cause of anaphylaxis in children. The disease, like other atopies, appears to be familial. Genetic and environmental factors (e.g., diet in infancy, aeroallergens and geography) predispose to food allergy. Methods This a cross sectional study. To assess which characteristics were associated with food allergy, we conducted simple logistic regressions of each type of atopy with food allergy as the dependent variable. A p<0.05 was considered significant. In the data modeling, we did not assume any hierarchical effects of families and schools on the food allergy status of participating children. Therefore, logistic regression with fixed effects only was used in modeling the data. Stepwise multilogistic regression with forward entry was used to determine a subset of characteristics that predicts best the presence of food allergy within the target population. Data were analyzed using SPSS statistical package (version 18). Results Three hundred ninety-seven children (205 female) were enrolled on the study. The mean (SD) age was 7.2 (1.1) years. Two hundred seventy-one (68.2%) were fed solely human milk, 122 (30.7%) were fed human milk supplemented with cow milk protein-based formulas. Significant associations were present between childhood food allergy and personal atopic dermatitis (p<0.001), asthma (p <0.001) and rhino-conjunctivitis (p<0.05). Significant associations present between childhood food allergy and an immediate family member with food allergy, asthma, atopic dermatitis, or rhino-conjunctivitis. The best predictors of food allergy were personal atopic dermatitis (p=0.000), personal asthma (p=0.000), father with atopic dermatitis (p=0.005) and father with rhino-conjunctivitis (p=0.012).

Use of Soy Protein-Based Formulas in Infant Feeding

Soy protein-based formulas have been available for almost 100 years. Since the first use of soy formula as a milk substitute for an infant unable to tolerate a cow milk protein-based formula, the formulation has changed to the current soy protein isolate. Despite very limited indications for its use, soy protein-based formulas in the United States may account for nearly 25% of the formula market. This report reviews the limited indications and contraindications of soy formulas. It will also review the potential harmful effects of soy protein-based formulas and the phytoestrogens contained in these formulas.

Growth, Tolerance and Biochemical Measures in Healthy Infants Fed a Partially Hydrolyzed Rice Protein-Based Formula: A Randomized, Blinded, Prospective Trial

Objective: To evaluate growth, tolerance and plasma biochemistries in infants fed an experimental rice protein-based infant formula.Design: Randomized, blinded, 16 week parallel feeding trial of 65 healthy infants fed either an experimental partially hydrolyzed rice protein-based infant formula fortified with lysine and threonine (RPF, n = 32), or a standard intact cow’s milk protein-based formula (CMF, n = 33) as a control. Assessments occurred at enrollment (average 2 days), 2, 4, 8, and 16 weeks of age.Results: Growth as indicated by weight, length, and head circumference was not different between the 2 formula groups. All plasma biochemistries for both groups were within reference normal range. However, RPF group had lower phosphorus and urea nitrogen, lower essential amino acids except threonine, which was higher, and lower ratio of essential (including semi-essential) to non-essential amino acids. Differences in the concentrations and ratios of amino acids became less as feeding progressed with age. Plasma total protein, albumin, prealbumin, calcium, magnesium, and alkaline phosphatase were not different between groups.Conclusion: Healthy infants fed an experimental partially hydrolyzed rice protein-based formula had normal growth, tolerance, and plasma biochemistry comparable to those of infants fed a standard intact milk protein-based formula, despite some differences in amino acid profiles.

Release of angiotensin converting enzyme-inhibitory peptides by simulated gastrointestinal digestion of infant formulas

The angiotensin converting enzyme (ACE)-inhibitory activity of several infant formulas was evaluated. Most of these products showed moderate inhibitory activity, but two exceptions that corresponded to an extensively hydrolysed whey formula and an extensively hydrolysed casein formula were detected. Two products (a non-hydrolysed milk protein-based formula and an extensively hydrolysed whey formula) were subjected to a two-stage in vitro enzymatic procedure, which simulates physiological digestion, in order to study the impact of digestion on ACE-inhibitory activity. The ACE-inhibitory activity of the non-hydrolysed formula increased during simulated gastrointestinal digestion, while no significant change was observed in the activity of the hydrolysed whey formula prior to and after, digestion. The peptides generated from these two products during simulated physiological digestion were sequenced by tandem spectrometry. At the end of the digestion, most peptides found in the non-hydrolysed milk protein-based formula were formed during incubation with the pancreatic extract, but, in the hydrolysed whey formula, many peptides present in the undigested product survived simulated digestion. The potential ACE-inhibitory activity of these peptides is discussed with regard to their amino-acid sequences.

Nutritional Management of Neonatal and Infant Liver Disease

After completing this article, readers should be able to: 1. Describe the caloric requirements of a neonate who has chronic liver disease. 2. Identify the vitamin and mineral deficiencies associated with cholestasis and the methods used to correct these deficits. 3. Describe the relationship between total parenteral nutrition and the development of chronic liver disease. 4. Delineate the relationship between malnutrition at the time of liver transplantation and subsequent morbidity and mortality. 5. List the best measurements of nutrition assessment in infants who have chronic liver disease. The liver is involved in many of the body’s metabolic processes, including: regulation of protein, fat, and carbohydrate metabolism; vitamin storage and activation; and detoxification and excretion of waste products. The healthy liver synthesizes and excretes bile salts. With cholestatic liver diseases, poor bile flow results in fat malabsorption because micelles, which solubilize long-chain fatty acids, cannot form without bile salts. Fat malabsorption results in enteric losses of the fat-soluble vitamins A, D, E, and K. Impaired liver function can lead to nutrient deficiencies and eventually protein-energy malnutrition. All of these factors, combined with the common symptoms of anorexia and poor dietary intake, make malnutrition common in chronic liver disease, particularly if it occurs in infants, who are more vulnerable to the debilitating effects of malnutrition because of their higher energy and growth requirements. A wide range of deficits occurs in most chronic liver diseases of children (Table 1⇓ ). Malnutrition itself may induce further derangements of liver function because the liver requires energy for a number of synthetic, storage, and detoxification functions. View this table: Table 1. Nutritional Risk Factors in Acute and Chronic Liver Disease The need for aggressive, early nutrition support in neonates has been well established and discussed extensively. Some centers routinely use a “standardized” approach to nutrition support; we use a “tailored” approach that entails parenteral or …

The lessons of noninterventional and interventional prospective studies on the development of atopic disease during childhood.

The lessons of noninterventional and interventional prospective studies on the development of atopic disease during childhood.

Bone mineralization and growth in term infants fed soy-based or cow milk-based formula

The purpose of this study was to evaluate the adequacy of a soy protein-based formula versus a cow milk protein-based formula for body growth and skeletal mineralization in the first year of life. Thirty-six healthy, term, appropriate for gestational age infants were assigned randomly and prospectively to one of two feeding groups and observed longitudinally over the first year of life. Group 1 infants (n = 18) were fed soy protein isolate-based formula (Isomil with Iron); group 2 infants (n = 17) were fed a cow milk protein-based formula (Similac with Iron). All infants were given the formula within the first 24 hours of life, and were fed the study formula through the first year of life. Weight, length, and head circumference were recorded; bone mineral content (BMC) and bone width (BW) were measured at one-third distal length (midshaft) of the left radius and ulna during the first 18 days of life, and again at 6 weeks, and 3, 6, 9, and 12 months postnatally. Baby food was provided to all infants, and except for type of formula, food intake was similar for all infants. Weight, length, and head circumference were normal in all infants and not different between groups. BMC and BMC/BW were similar for both groups at entry into the study. Group 1 infants had significantly lower BMC and BMC/BW at 3, 6, 9, and 12 months of age (P less than 0.05 to P less than 0.0001) compared with group 2 infants, but their values were similar to those in previously studied infants receiving human milk with vitamin D supplementation. The long-term implication of differences in bone mineralization in early infancy for long-term skeletal mineralization remains to be determined.

Cows' milk protein-sensitive enteropathy. An important factor in prolonging diarrhoea of acute infective enteritis in early infancy.

The possible role of cows' milk protein in prolonging diarrhoea in very young infants with acute infective enteritis was studied in 14 infants, 9 under the age of 2 months and 5 older than 6 months. Bacterial pathogens were isolated from the stools of 4 infants from the younger age group. After appropriate initial treatment the infants were maintained on a cows' milk protein-free formula. 6 weeks later jejunal biopsies were performed before and 24 hours after challenge with a low lactose cows' milk protein formula. The immunoglobulin and complement levels in the serum and duodenal juice were also estimated at these times. Attempts to isolate bacterial and viral pathogens in stools were again made in all patients. The 5 older infants clinically tolerated cows' milk protein and their pre- and postchallenge jejunal biopsies were within normal limits. However, significant histological changes were observed in the postchallenge jejunal biopsies of all 9 infants under 2 months of age. In addition, 5 of these infants developed diarrhoea. This suggests that the jejunal mucosa of very young infants previously fed a cows' milk protein-based formula and who contract infective enteritis suffers damage when rechallenged with cows' milk protein.