Milk-based Formula Research Articles

Assessing solubility of meloxicam in age-specific gastric and intestinal media relevant to adults and pediatric populations: implications for optimizing dosing in patients for postoperative pain

BackgroundOral dose formulations must be soluble in gastrointestinal fluids for systemic absorption. The solubility of meloxicam was determined in 16 different age-specific simulated gastric and intestinal media that mirrored the microenvironments in pediatrics and adults.MethodsThe solubility of meloxicam in the 16 different age-specific simulated gastric and intestinal biorelevant media was assessed using the standard US pharmacopeial method. The molecular descriptors of meloxicam were used to assess its intestinal permeability.ResultsMeloxicam exhibited low solubility in the age-specific simulated gastric media for fasted and fed states and in pediatrics and adults. Similarly, meloxicam exhibited low solubility in the age-specific simulated media that mirrored neonates fed cow milk-based formula. On the other hand, meloxicam exhibited high solubility in the rest of the age-specific pediatric and adult intestinal media that simulated the fasted and fed states. The pediatric-to-adult solubility ratios were outside the 80–125% range in 7 (58.3%) and was borderline in 1 (8.3%) out of the 12 calculated ratios. These findings indicated that the solubility of meloxicam showed clinically significant differences in 8 (66.7%) of the compared media.ConclusionMeloxicam exhibited low solubility in the age-specific simulated gastric media and high solubility in the simulated intestinal media for adults and pediatrics. Moreover, the pediatric-to-adult solubility ratios may have clinically significant implications. These differences can be translated into a higher likelihood of failing to demonstrate bioequivalence of different formulations containing meloxicam and variabilities in the performance of these formulations.

Microbiota, metabolic profiles and immune biomarkers in infants receiving formula with added bovine milk fat globule membrane: a randomized, controlled trial.

Few studies have evaluated the effects of milk fat globule membrane (MFGM) on microbiota and immune markers in early infant nutrition. In this double-blind randomized study, infants (7-18 days of age) received either bovine milk-based infant formula (Control) or similar formula with an added source (5 g/L) of bovine MFGM (INV-MFGM) for 60 days. A reference group received mother's own human milk over the same period (HM). Oral and stool samples were collected (Baseline and Day 60) to evaluate microbiota, immune markers, and metabolites. At Day 60, stool bacterial diversity and richness were higher in formula groups vs HM, as were Bifidobacterium bifidum and B. catenulatum abundance. Compared to HM, stool pH was higher in Control, while acetate, propionate, isovalerate, and total short- and branched-chain fatty acids were higher in INV-MFGM. Butyrate and lactate increased for INV-MFGM from baseline to Day 60. No group differences in oral microbiota or immune markers (α- and β-defensin, calprotectin, or sIgA) were detected, although sIgA increased over time in all study groups. Added bovine MFGM in infant formula modulated stool microbiota and short- and branched-chain fatty acids compared to human milk; changes were modest relative to control formula. Overall, distinct patterns of stool metabolites and microbiota development were observed based on early nutrition. ClinicalTrials.gov, identifier NCT04059666.

Preliminary risk assessment of exposure to 3-monochloropropanediol and glycidyl fatty acid esters from infant formula and baby food products on the Saudi market

3-Monochloropropanediol fatty acid esters (3-MCPDE) and glycidyl esters (GE) are well-identified processing-induced chemical toxicants detected in infant formula and baby foods worldwide. We analysed the levels of 3-MCPDE and GE in infant formula and baby food products available in Saudi Arabia, followed by a dietary risk assessment for exposure to these contaminants in infants and young children from birth to 3 years. Eighty-five commercial infant formulas (n = 35) and baby foods (n = 50) available for consumption by infants and babies purchased from the Saudi market during 2022 were analysed for these contaminants using gas chromatography-tandem mass spectrometry. 3-MCPDE and GE were detected in 100 and 80% of the samples, with a mean concentration of 57 µg/kg (range: 2–285 µg/kg) and 30 µg/kg (range: not detected–217 µg/kg), respectively. The highest concentration was found in milk-based formula for infants 0–6 months (285 µg/kg) and the lowest was found in fruit purees (2 µg/kg). Preliminary exposure and risk assessment showed increased exposure to 3-MCPDE for infants exclusively fed infant formula with exposure declining with age due to the introduction of solid foods. GE exposure levels reached 0.8 µg/kg body weight per day, which declined over time with margin of exposure values below 25,000. These results indicate that the levels of 3-MCPDE and GE in infant formula may pose potential risks to infants exclusively fed formula; therefore, adopting EU regulations should reduce the presence of these processing contaminants in essential infant foods.

Lipidomics of sheep and goat Milk-based infant formulae during in vitro dynamic digestion

Lipid hydrolysis process during IF digestion, particularly the characterization of the lipidome and the resulting lipid breakdown products, has not been thoroughly investigated. This study aimed to compare the lipid hydrolysis profiles during the in vitro dynamic digestion of IFs made from whole sheep and goat milk. Using a lipidomics platform and multivariate statistical analysis, we observed changes in complex lipid levels during digestion. In the gastric compartment, we noted a progressive hydrolysis of triacylglycerols, phosphatidylcholines, and sphingomyelins. Conversely, lipolysis breakdown products like monoacylglycerols (e.g., MG(16:0), MG(18:0)), diacylglycerols, lysophosphatidylcholines (LPC 16:0, LPC 18:1, LPC 18:2), and free fatty acids increased in the intestinal compartment. The lipolysis trends were similar for both types of infant formulas, with long-chain fatty acid triglycerides (C > 46) exhibiting lower digestibility compared to medium-chain fatty acid triglycerides. Overall, these results indicate that sheep milk can be used as an ingredient in the manufacturing of IF.

A collectanea of food insulinaemic index: 2023

Background and AimsTo systematically update and publish the lnsulinaemic Index (II) value compilation of food/beverages. MethodsA literature search identified around 400 scholarly articles published between inception and December 2023. II values were pooled according to the selection criteria of at least 10 healthy, non-diabetic subjects with normal BMI. In addition, the II reported should have been derived from incremental area under the curve (iAUC) calculation of the insulin concentration over time. The reference food used from the pooled articles were either glucose or bread. ResultsThe II of 629 food / beverage items were found from 80 distinct articles. This is almost a five-fold increase in the number of entries from a previous compilation in 2011. Furthermore, these articles originated from 32 different countries, and were cleaved into 25 food categories. The II values ranged from 1 to 209. The highest overall recorded II was for a soy milk-based infant formula while the lowest was for both acacia fibre and gin. Upon clustering to single food, the infant formula retained the highest II while both acacia fibre and gin maintained the lowest recording. As for mixed meal, a potato dish served with a beverage recorded the highest II while a type of taco served with a sweetener, vegetable and fruit had the lowest II. Our minimum and maximum II data values replace the entries reported by previous compilations. ConclusionAcknowledging some limitations, these data would facilitate clinical usage of II for various applications in research, clinical nutrition, clinical medicine, diabetology and precision medicine. Future studies concerning II should investigate standardisation of reference food, including glucose and the test food portion. Although this collectanea adds up new food/beverages II values, priority should be given to populate this database.

Food interventions and nutritional status of undernourished children ages 0-5 years old in southern Philippines: a systematic review and meta-analysis

Abstract This review aims to provide a comprehensive synthesis and determine pooled effectiveness of food interventions on the nutritional status of undernourished children ages 0-5 years old in low- and middle-income countries. Specific objectives include identification, selection, and appraisal of interventions that target undernourished children ages 0-5 years old. This study included Randomized Controlled Trials, Pre-post Interventional, Case-Control, and Cohort Studies that were conducted from 2016-2019 that target Undernourished children, 0-5 years old. The outcome is improvement in Nutritional Status: Weight-for-age, Length-for-age, Weight-for-length, Weight Gain, Mean Weight, Mid-Upper Arm Circumference, Length (cm). The search and identification of studies, supplemented with the inclusion and exclusion criteria, was done through an online database (Pubmed, Ebscohost, ScienceDirect, and Google Scholar) and in the Department of Agriculture Library. The study used four (4) tools in appraising the studies. The four tools differed in terms of their indication of use by study design: Risk of Bias-2 for Randomized Controlled Trials (RCTs), Risk of Bias in Non-Randomized Studies- of Interventions for Non-Randomized Studies (NRSI), and Heller’s Public Health Checklist for quasi-experimental (within-group) designs. Out of thirty-one (31) studies, this paper compiled seven (7) interventions. The interventions are local and homemade food, nutritional education, food production, milk-based formula, reduced dose of RUTF, rehabilitation programs, and positive deviance approach. Risk of Bias: (ROB-2) 100% of the studies have low risk in random sequence generation, blinding of outcome assessment, and selective reporting domains. Only 10% of the studies demonstrated unclear or moderate risk under attrition bias due to incomplete outcome data. Roughly 20% of the studies also showed unclear or moderate risk under selection and performance bias. (ROBINS-I) 67% (6/9) of the included studies are low risk for overall bias. (Heller) Studies were appraised by Heller’s checklist where identification of strengths and weaknesses were identified. This review found that local and homemade food improves the nutritional status of undernourished children below five years old. Findings show that nutrition education has little to no effect, while food production needs more studies to increase its certainty. Other interventions mentioned need more similar studies to obtain a pooled effectiveness. This review has excluded studies that are of high risk of bias to minimize low certainty of evidence. However, this review was unable to examine adverse effects of the interventions. This review has some studies not pooled due to missing values such as standard deviations and confidence interval.

Characterisation and comparison site-specific N-glycosylation of whey proteins from donkey and human colostrum and mature milk using glycoproteomics

Although the composition of donkey milk is similar to that of human milk, systematic comparisons of the site-specific N-glycosylation patterns of their whey proteins are lacking. In this study, hydrophilic interaction chromatography-based enrichment of intact N-glycopeptides, coupled with a site-specific glycoproteomics strategy, was used to systematically characterise whey N-glycoproteins in donkey colostrum (DC), donkey mature milk (DM), human colostrum (HC), and human mature milk (HM) for the first time. We identified 628, 347, 868, and 425 site-specific N-glycans mapped to 135, 67, 113, and 60 glycoproteins in DC, DM, HC, and HM, respectively. Bioinformatic analysis revealed the potential biological effects of N-glycosylation modifications on the whey proteins themselves. Our findings elucidated the composition of donkey and human milk whey N-glycoproteins and their potential structure-activity relationships and provided guidance for the production of specific functional donkey milk products and the development of donkey milk-based infant formulas.

Enteral Agonism of the Farnesoid X Receptor-Fibroblast Growth Factor 19 Axis Prevents Cholestasis in TPN-Fed Piglets

Total parenteral nutrition (TPN) administration provides necessary nutrients to infants who cannot tolerate enteral feedings. However, the use of TPN can result in cholestasis which can cause parenteral nutrition-associated liver diseases. Previous mitigation strategies for cholestasis have included administering bile acids enterally to encourage normal bile acid metabolism. The objective of this study was to determine if treatment of either ursodeoxycholic acid (UDCA), Tropifexor (TPX), or fibroblast growth factor 19 (FGF19) will prevent cholestasis in a piglet TPN model through the activation of the farnesoid X receptor (FXR)-FGF19 axis. We hypothesize that UDCA will have minimum effects on FXR while TPX, a potent FXR agonist, will significantly affect the FXR pathway, and FGF19 will reduce bile acid synthesis to alleviate cholestasis. Piglets received TPN for 3 weeks and were treated enterally with either UDCA (25 mg/kg*day) or TPX (7.5 μg/kg*day) with minimal milk-based formula (12 mL/kg*day), or daily intravenous FGF19 (0.25 mg/d) injection. Body weight gain was not different after 3 weeks. Plasma markers of cholestasis such as of total bile acids, bilirubin, and gamma-glutamyl transferase were lower in pigs that received TPX compared to the control treatment at the end of the study. Circulating levels of FGF19 and tissue concentrations of total bile acids were not different across treatments. In the ileum, TPX increased mRNA expression of FGF19, ileal lipid binding protein, and organic solute transporter α compared to the control pigs. All treatments reduced the mRNA expression of apical sodium-dependent bile acid transporter compared to the control treatment. TPX also increased mRNA expression of small heterodimer protein and bile salt export pump in the liver. Overall, we conclude that UDCA and FGF19 had minimal effects on cholestasis, whereas TPX prevented cholestasis in part via activation of the FXR-FGF19 axis in TPN fed piglets. NIDDK R01-DK094616 K01 DK129408 T32 NIH grant DK07664. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Determination of the Fatty Acid Profile and Lipid Quality Indices in Selected Infant Formulas.

The quality of fat in infant milk is determined by the fatty acid profile and selected indices describing nutritional value. The aim of this study was to analyze the fatty acid profile and lipid quality indices of infant formulas and compare these data with breast milk. The study material included seven types of cow's milk-based follow-on infant formulas and samples of mature breast milk. The determination of fatty acids was performed using the gas chromatography (GC) technique. Lipid quality indices were calculated based on the relevant equations. Infant formulas contained more medium-chain fatty acids (MCFAs) and oleic acid. Moreover, they contained more than 30% more linoleic acid and more than twice as much α-linolenic acid and docosahexaenoic acid. In contrast, significant amounts of trans fatty acids (TFAs) were noted in breast milk, while infant formulas contained trace amounts. Infant formulas were characterized by a lower AI (Index of Atherogenicity) (0.49-0.98) and TI (Index of Thrombogenicity) (0.48-0.60) and a higher H/H (hypocholesterolemic/hypercholesterolemic) ratio (1.93-2.30) compared with breast milk (1.47, 1.60, and 1.21, respectively). The composition of infant formulas depended on the type of fat added at the production stage and differed significantly from breast milk, particularly in terms of polyunsaturated fatty acids and lipid quality indices.

Evaluation of Streptococcus mutans Biofilm Formation and Acidogenicity of Infant Milk Formulas for Treating Cow Milk Allergy: An in vitro Study

Introduction: When infants cannot consume breast milk, the most commonly available alternative milk formula is cow milk-based. Due to a rise in the prevalence of cow milk protein allergy (CMPA) among children, this study aimed to assess the biofilm formation and acidogenicity of cow milk-based formulas as well as milk formulas suggested for children with CMPA. Methods: Cow milk-based formulas with 0%, 10%, or 18% sucrose added, partially hydrolyzed formula (pHF), extensively hydrolyzed formula (eHF), amino acid-based formula (AAF), and soy-based formulas with 0%, or 11% sucrose added were evaluated. Streptococcus mutans was used as a representative microorganism associated with caries. The acidogenicity after 24-h incubation was assessed by the pH of the formed biofilm and lactic acid formation. Biofilm formation was quantified using crystal violet staining. Additionally, the biofilm characteristics were determined using confocal laser scanning microscopy (CLSM). Comparisons were made among formulas without added sucrose to observe protein-based differences. Furthermore, formulas with different sucrose percentages were compared to explore the impact of sucrose content. Results: When comparing the formulas without added sucrose, the biofilm formation in the cow milk-based formula and pHF were significantly greater than the soy-based formula, eHF, and AAF. In the presence of S. mutans, all formulas reduced the biofilm pH below the critical enamel pH. The cow milk-based formula and AAF showed a significantly lower biofilm pH than the pHF, soy-based, and eHF groups, while the lactic acid production was markedly higher in the cow milk-based formula, pHF and AAF, compared with the eHF and soy-based formula. Adding sucrose into the cow milk-based and soy-based formulas substantially increased biofilm mass. The biofilm pH of the cow milk-based formulas, with or without sucrose, was significantly lower than that of the soy-based formulas. The CLSM indicated distinct biofilm characteristics among the different protein-based formulas, with sucrose supplementation promoting S. mutans aggregation in cow milk-based formula biofilm and increased density and intact biofilm in the soy-based formula. Conclusion: All assessed milk formulas had caries-inducing factors, including those without supplemental sucrose. Among them, the eHF demonstrated the least caries-inducing factors, attributed to its minimal biofilm formation and the highest biofilm pH.

Plasma Sphingomyelins and Carnitine Esters of Infants Consuming Whole Goat or Cow Milk-Based Infant Formulas or Human Milk

BackgroundInfant formulas are typically manufactured using skimmed milk, whey proteins, and vegetable oils, which excludes milk fat globule membranes (MFGM). MFGM contains polar lipids, including sphingomyelin (SM). ObjectiveThe objective of this study was comparison of infant plasma SM and acylcarnitine species between infants who are breastfed or receiving infant formulas with different fat sources. MethodsIn this explorative study, we focused on SM and acylcarnitine species concentrations measured in plasma samples from the TIGGA study (ACTRN12608000047392), where infants were randomly assigned to receive either a cow milk-based infant formula (CIF) with vegetable oils only or a goat milk-based infant formula (GIF) with a goat milk fat (including MFGM) and vegetable oil mixture to the age ≥4 mo. Breastfed infants were followed as a reference group. Using tandem mass spectrometry, SM species in the study formulas and SM and acylcarnitine species in plasma samples collected at the age of 4 mo were analyzed. ResultsTotal SM concentrations (∼42 μmol/L) and patterns of SM species were similar in both formulas. The total plasma SM concentrations were not different between the formula groups but were 15 % (CIF) and 21% (GIF) lower in the formula groups than in the breastfed group. Between the formula groups, differences in SM species were statistically significant but small. Total carnitine and major (acyl) carnitine species were not different between the groups. ConclusionsThe higher total SM concentration in breastfed than in formula-fed infants might be related to a higher SM content in human milk, differences in cholesterol metabolism, dietary fatty acid intake, or other factors not yet identified. SM and acylcarnitine species composition in plasma is not closely related to the formula fatty acid composition.This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12608000047392

Ameliorating effect of 2′-fucosyllactose and 6′-sialyllactose on lipopolysaccharide-induced intestinal inflammation

Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL co-treatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pre-treatment HMO mixture in vitro; thus, this ratio was selected and used for low, middle, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as body weight loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggested that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.

Comparison of glycation and glycosylation level between bovine milk-based and goat milk-based infant formula through label-free proteomics techniques

Heat treatment is unavoidable in the processing of infant formula; however, heat treatment causes the proteins to undergo Maillard reaction and form glycation products, which can negatively affect the nutrition and function of the protein. At the same time, glycosylation is a broad post-translational protein modification that is important in a variety of biological processes. However, glycated proteins as well as N-glycoprotein components in infant formula have not been well characterized. Here, a comprehensive comparative analysis of the glycated proteome as well as the N-glycosylated proteome was conducted in both bovine milk-based (BF) and goat milk-based (GF) infant formula. In total, 918 whey proteins were identified from the whey fraction, including 200 glycated proteins and 219 glycosylated proteins. Furthermore, 33 N-glycosylated proteins containing 101 N-glycosylation sites and 64 glycosylated peptides derived from 30 proteins were significantly different (p < 0.05) between BF and GF. Most of the significantly different proteins are associated with innate immunity as well as defense responses. With respect to the differences between BF and GF, ɑ-lactalbumin (LALBA) had higher glycation level in BF than GF; whereas β-lactoglobulin (LGB) had higher glycation level in GF than BF. For glycosylation level, transferin (TF) was highly glycosylated in GF than BF; while serum albumin (ALB) was highly glycosylated in BF than GF. Our results elucidated the proteome, glycated proteome, N-glycosylated proteome in bovine milk-based and goat milk-based infant formulas, which may be useful to researchers in related fields and provide guidance on the improvement of processing technology for infant formula.

Worldwide Variations in Fluoride Content in Beverages for Infants.

In situations where breastfeeding is impractical, milk formulas have emerged as the primary choice for infant nutrition. Numerous global studies have scrutinized the fluoride content in these formulas, uncovering fluctuations in fluoride levels directly associated with the method of preparation. This variability poses a potential risk of elevated fluoride concentrations and, consequently, an increased susceptibility to dental fluorosis in infants. The primary objective of this review is to intricately delineate the fluoride content in dairy formulas and emphasize the variability of these values concerning their reconstitution process. The review's findings reveal that, among the 17 studies assessing fluoride levels in infant formula, milk-based formulas exhibit a range of 0.01-0.92 ppm, with only two studies exceeding 1.30 ppm. Conversely, soy-based formulas demonstrate values ranging from 0.13-1.11 ppm. In conclusion, the observed variability in fluoride levels in infant formulas is ascribed to the choice of the water source employed in the preparation process. This underscores the paramount importance of meticulously adhering to recommendations and guidelines provided by healthcare professionals concerning the utilization of these formulas and their meticulous reconstitution.

Review on Key Features of Infant Feeding: Human Milk and Infant Formula

Human breast milk (HBM) is the finest source of nutrition for almost all infants. Breast milk as a bodily fluid has many benefits beyond somatic cell growth, including regulation of postnatal intestinal function, immune ontogeny, and brain development. However, breastfeeding is strongly recommended, breastfeeding may not always be possible, suitable or solely adequate1. Hence, Infant formula is often an alternative source of infant nutrition when breastfeeding is unacceptable or impossible. The composition of infant formula should be as close as possible to the composition of human breast milk, both in terms of content and chemical specification2. Infant formulas try to mimic the nutritional composition of breast milk as closely as possible. A number of substitutes to milk-based formula also exist. In this article, we review nutritional information for breast milk and infant formulas to help you better understand the importance of breastfeeding and the use of infant formulas up to 24 months of age when alternative feeding is required. In general, breast milk is the ideal food to ensure that an infant's nutritional needs are met.&#x0D; Keywords: breast milk; infant formula; type of infant formula; benefits

Literature Review: Infant formulas with human milk oligosaccharides on gut microbiome and intestinal immune system

Background: Infant formula has a similar composition to breast milk, especially on key components like proteins, fats, and functional oligosaccharides. However, significant differences exist between bovine milk-based formula and human breast milk, particularly in the abundance and diversity of human milk oligosaccharides (HMOs). HMOs are pivotal in shaping the infant gut microbiome and immune system, with potential implications for infant health and development.Objectives: The literature review aimed to explore the role of HMOs in shaping the gut microbiome and strengthening the intestinal immune system in infants.Methods: Descriptive research was carried out in May-August 2023 using the literature review method. The design and implementation of this study referred to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for Randomized Controlled Trials (RCTs). Literature sources were obtained from PubMed, Elsevier, Medline, Nature, PLOS, MPDI, JAMA, and Scopus publication databases with a limitation of the last ten years (2013-2023). One hundred twenty articles were obtained with these keywords and then selected in stages according to predetermined criteria. Six articles that met the criteria were retrieved from 2013-2023. The articles obtained were compiled, analyzed, and concluded by looking for similarities and dissimilarities, giving views, comparing, and summarizing.Results: The review revealed that HMOs significantly influenced the composition and function of the infant's intestinal microbiota, inhibiting harmful pathogens in the intestine. Therefore, HMOs as prebiotics were crucial in promoting intestinal immune system health in infants.Conclusion: Human Milk Oligosaccharides (HMOs) in infant formula substantially impacted the gut microbiome composition and the infant's intestinal immune system. Studies consistently showed that HMOs influenced the growth and diversity of gut bacteria, leading to outcomes similar to those seen in breastfed infants.

Lactoferrin in breast milk-based powders.

This study aimed to determine lactoferrin (LF) in breast milk-based powders and formulas. Lactoferrin is an important whey protein in all mammalian milks and is responsible in large part for the known antimicrobial effects of human milk in particular. As breast feeding is not always possible, formulas based on cows milk have been developed in order to meet the nutritional needs of the newborn, while more recently human breast milk-based powders have been introduced to offer the biological functionality of human milk to pre-term and critically ill babies. In the present work, the amount of LF in commercial breast milk-based powders was tested by a validated RF-HPLC method for the determination of LF in breast milk in order to examine both the applicability of the method but at a second level the amount of LF in these commercial products. The detection of LF was possible but the complexity of the matrix lead us to the use the standard addition methodology in order to achieve quantification. The results indicated that breast milk-based powders had higher amount of LF than cows milk-based formulas, both non-fortified and fortified.

Quantitation of bioactive components in infant formulas: Milk oligosaccharides, sialic acids and corticosteroids

Human milk is considered the optimal food for infants with abundant nutrients and bioactive components, which play key roles in infant health and development. Infant formulas represent appropriate substitutes for human milk. There are many brands of infant formula with different ingredient sources and functions on the market. The present study aims to quantify important bioactive components, i.e., milk oligosaccharides (MOS), sialic acids (Sia) and corticosteroids, in different infant formulas and compare these to human milk. In total, 12 different infant formulas available on the Dutch market were analyzed in this study. The concentrations of MOS and Sia were characterized by UHPLC-FLD and LC-MS, while corticosteroids were determined using established UHPLC-MS/MS methods. Among infant formulas, 15 structures of oligosaccharides were identified, of which 2′-Fucosyllactose (2′FL), 3′-Galactosyllactose (3′GL) and 6′-Galactosyllactose (6́′GL) were found in all infant formulas. The oligosaccharide concentrations differed between milk source and brands and were 3–5 times lower than in human milk. All infant formulas contained Sia, N-acetylneuraminic acid (Neu5Ac) was dominant in bovine milk-based formulas, while N-glycolylneuraminic acid (Neu5Gc) was major in goat milk-based formula. All infant formulas contained corticosteroids, yet, at lower concentrations than human milk. Insight in concentrations of bioactive components in infant formula compared to human milk may give direction to dietary advices and/or novel formula design.

Homogenization and thermal processing reduce the concentration of extracellular vesicles in bovine milk.

Extracellular vesicles (EVs) in bovine milk confer beneficial physiologic effects to consumers. Industrial processing treatments may affect the amount or bioactivity of EVs intrinsic to bovine milk. We investigated how the content and concentration of EVs were affected by homogenization and thermal processing of raw bovine milk. Raw milk was processed by homogenization, low-temperature (LT) heat, or pasteurization [high-temperature short-time (HTST) and ultra-high-temperature (UHT)] in a pilot processing facility. EVs were isolated from the raw and processed bovine milk using differential ultracentrifugation and quantified using a nanoparticle tracking analyzer. Bovine milk EVs were assessed for total miRNA and protein concentrations standardized to particle count using a fluorometric assay. There were 1.01 × 1010 (±3.30 × 109) EV particles per ml of bovine milk. All industrial processing treatments caused >60% decrease in EV concentration compared to the raw bovine milk. Homogenization and heat treatments independently and additively reduced the content of EVs in bovine milk. The averages of total miRNA/particle and total protein/particle concentrations were elevated threefold by low-temperature heat-processing treatment relative to HTST and UHT pasteurizations. The average diameter of EVs was reduced by 11%-16% by low temperature compared to raw milk (127 ± 13 nm). Homogenization and pasteurization indiscriminately reduce the EV concentration of bovine milk. Smaller EVs with higher protein content resist degradation when processing bovine milk at sub-pasteurization temperature. This new foundational knowledge may contribute to food product development on the preservation of EVs in processed dairy products, including bovine milk-based infant formulas that some newborns are dependent on for adequate growth and development.

What is Known About Cow's Milk Protein Allergy in Preterm Infants?

Background: Cow's milk protein allergy (CMPA) is well described in term infants, as opposed to preterm infants. In preterm infants, CMPA shares many gastrointestinal symptoms with necrotizing enterocolitis (NEC). Objectives: To evaluate the presentation of CMPA in preterm infants and to investigate the different diagnostic and therapeutic options. Materials and Methods: We searched for the relevant literature using the medical databases PubMed, Web of Science, and the Cochrane Library. We performed a post hoc analysis on the 25 case reports included in this study. Results: Literature was scarce and heterogeneous. The majority of preterm infants with CMPA were exposed to bovine-based milk proteins before the development of symptoms. The most common clinical manifestations were bloody stools, vomiting, and abdominal distension. Of the 25 cases, only 7 (28%) retained human milk in their diet after diagnosis. In the larger studies, no study has human milk as primary feeding choice after diagnosis. Conclusions: Preterm infants exposed to a type of cow's milk-based formula in their first days of life have a higher risk of developing CMPA. Most of the preterm infants are no longer fed with human milk after the diagnosis of CMPA is made, which is in contrast with current nutrition guidelines in preterm infants. We strongly advocate that human milk with mothers on a cow's milk-free diet is the first choice of feed after the diagnosis of CMPA. Prospective studies are necessary to obtain more information regarding clinical presentation, diagnostic tools, and therapeutic approaches.