Search Results (915)

Background: The 2025–2030 Dietary Guidelines for Americans recommend that 6–12-month-old infants receive 11 mg iron/day. The contribution of iron-rich foods in meeting guidelines is unclear. Objectives: The aims were to: (1) determine the contribution of iron-fortified cereal, infant formula and heme-iron sources to infants’ total dietary iron intake; (2) examine differences in iron adequacy by milk-feeding type; and (3) identify feeding patterns associated with meeting daily iron requirements through dietary sources. Methods: Mothers of infants were recruited from a pediatric clinic and 24 h feeding recalls were conducted to estimate infants’ iron intake. Infants’ milk-feeding types were: breastmilk only (BF), mixed (MF), or infant formula only (FF). Main outcomes were: meeting/not meeting daily iron requirement (11 mg) overall and by milk-feeding type; contribution of iron-fortified infant cereal, formula and meat to daily iron intake. Descriptive statistics, bivariate chi-square tests, and multivariate logistic regression analyses were conducted. Results: Most participants identified as African American or Hispanic (76%) and were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (84%). Thirty-nine percent consumed < 11 mg iron/day from dietary sources. By milk-feeding type, inadequate iron intake was significantly higher among the BF (72%) and MF (74%) groups vs. the FF group (24%, p < 0.05). Iron-fortified cereals were consumed by 46% of infants and provided a median iron intake of 6.75 mg. Among the FF group, infant formula provided 63% of the daily iron requirement. Conclusions: Inadequate dietary iron intake is common. Iron-fortified cereal is an important dietary iron source. Future research is warranted to understand the relations among infants’ daily iron intake, iron sources (heme vs. non-heme), and iron status. Full article

Toxicological risk assessment of food ingredients has traditionally relied on identifying a no-observed-adverse-effect level (NOAEL) or benchmark dose (BMD), followed by the application of default uncertainty factors (UFs) to derive health-based guidance values (HBGVs) such as the acceptable daily intake (ADI). While effective for conventional food additives, this approach may be inappropriate for nutrients and intrinsic food components with established physiological functions. This paper critically explores these limitations using free glutamate as a central example, alongside additional cases relevant to infant nutrition, including vitamin C, iodine, and human milk oligosaccharides (HMOs). Data on free glutamate in human milk show that breastfed infants habitually ingest amounts far exceeding additive-based ADIs without adverse effects, underscoring the limitations of applying default uncertainty factors and classical toxicological paradigms to endogenous nutrients. Comparable considerations apply to protein hydrolysates and amino acid-based infant formulas evaluated by EFSA, where growth, tolerance, and compositional suitability are integral to safety assessment. Overall, nutrient safety evaluation requires an integrative, physiology-informed framework that incorporates realistic exposure, developmental stage, and metabolic competence. Breast milk provides a biologically relevant reference, supporting a proportionate and science-based application of toxicological principles in infant nutrition. Full article

The milk fat globule membrane (MFGM) wraps around the surface of the milk fat globule, separating the internal lipid core from the external environment. MFGM is a complex trilayer membrane structure composed of polar lipids, sphingolipids, and functional proteins. In recent years, research on the biological characteristics of MFGM has been continuously deepening. It has triggered an exploration of the relationship between MFGM composition, structure, and functional mechanisms. This reveals the potential applications of MFGM in human health and production practices. This review systematically summarizes the composition and structure of MFGM, extraction and preparation techniques, functional mechanisms and the latest research progress in its applications in various fields. This study comprehensively compares the application scope of the MFGM extraction preparation technology. The mechanism of the biological activity of MFGM was further analyzed. Its application value in infant formula, dairy processing, functional foods, drug delivery systems, and cosmetics was evaluated. Nowadays, existing research needs to face numerous challenges, such as some components being unknown and the functional mechanisms not being clear enough. In the future, it is still essential to continuously pay attention to the research progress of MFGM. Further research is needed to accelerate the transformation of MFGM from by-products of dairy processing to multifunctional biomaterials. The purpose is to fully tap its enormous potential in nutrition, health care, and application fields. Full article

Background/Objectives: Gastroesophageal reflux disease (GERD) is prevalent in infants and frequently managed with acid-suppressive medications that elevate gastric pH. This pilot study aimed to evaluate how varying gastric pH levels (2.5, 4.0 and 6.0) influence the hydrolysis of milk proteins in human milk (HM), cow’s milk-based infant formula (CMF), and goat milk-based infant formula (GMF). Methods: Samples were subjected to a 30 min in vitro gastric digestion using pediatric human gastric juice obtained from clinical donors. Protein degradation was analyzed via SDS-PAGE densitometry, comparing digested aliquots to undigested controls. Results: At pH 2.5, caseins were highly digested in all samples, especially in HM and GMF. At pH 4.0, GMF displayed an apparent 51% greater casein degradation relative to CMF and HM in this pilot analysis. α-lactalbumin degradation was markedly higher in GMF at all pH levels; notably, at pH 4.0 and 6.0, only GMF exhibited digestion of this protein. Albumin showed almost complete degradation in HM and GMF at pH 2.5, and GMF maintained greater degradation at higher pH levels. β-lactoglobulin (absent in HM) was better digested in GMF at pH 2.5, whereas CMF showed higher hydrolysis observed at pH 4.0 and 6.0. Lactoferrin digestion was most efficient in HM and GMF at pH 2.5, with no differences observed at higher pH levels. Conclusions: These preliminary findings suggest that GMF may offer digestive advantages for infants with GERD under pharmacological acid suppression, particularly regarding casein and α-lactalbumin breakdown at higher pH. The distinct digestion kinetics of CMF and GMF at different pH levels provide a physiological basis for targeted infant feeding strategies. Further large-scale studies are required to validate these exploratory observations. Full article

Background/Objectives: Early postnatal nutrition is a modifiable determinant of brain maturation in preterm infants. Exclusive human milk-based diets (EHMD) are associated with improved neurodevelopmental outcomes. The objective of this exploratory ancillary analysis of the NEOVASC randomized controlled trial was to determine whether prolonging an exclusive human milk-based diet, specifically through continued human milk-based fortification until 36 weeks postmenstrual age, is associated with differences in early brain structure and functional motor development compared with earlier introduction of bovine milk-based fortifier or formula at 32 weeks postmenstrual age. Methods: This ancillary study of the NEOVASC trial included preterm infants (<32 gestational weeks and birthweight of 500–1250 g) randomized to either prolonged EHMD until 36 weeks PMA or a diet introducing bovine milk-based fortifier or formula from 32 weeks. Quantitative brain metrics, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were analyzed at 40 weeks PMA. Functional maturation was assessed repetitively using the General Movement Optimality Score (GMOS) (34, 36, and 40 weeks PMA) and Motor Optimality Score (52 weeks PMA). Results: Fifty-four infants were included. Groups did not differ in brain growth metrics. After adjustment for imbalances in clinical characteristics, no FA or ADC differences remained statistically significant. GMOS at 40 weeks PMA was higher in the intervention group, with no differences at other time points. Conclusions: In this exploratory ancillary analysis of the NEOVASC trial, prolonging an exclusive EHMD until 36 weeks postmenstrual age was not associated with consistent differences in early brain maturation or motor performance. Given the high overall exposure to human milk in both groups, subtle effects may have been attenuated. These findings require confirmation in larger, adequately powered studies with long-term follow-up. Full article

Introduction: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in early infancy and poses important clinical and economic challenges for affected children, their families, and healthcare systems. In Latin America, variability in diagnostic and therapeutic approaches remains substantial. Objective: We aim to systematically review the available evidence on CMPA, with emphasis on clinical characteristics, diagnosis, management, and economic impact, and to provide a complementary cost analysis of specialized formulas in the Colombian context. Methods: A systematic review was conducted according to PRISMA guidelines to synthesize current evidence on CMPA in pediatric populations. Studies published between 2010 and 2023 were screened using predefined eligibility criteria, and 46 studies were included in the qualitative synthesis. A complementary cost analysis was also performed to estimate the six-month costs associated with specialized infant formulas in Colombia, based on average age-specific formula consumption and standardized 2025 market prices. Results: The reviewed evidence confirms that CMPA is a heterogeneous condition with variable clinical manifestations and persistent diagnostic challenges, particularly in non-IgE-mediated presentations. Elimination of cow’s milk protein followed by oral food challenge remains the reference diagnostic approach. Breastfeeding with maternal dairy exclusion is consistently recommended as the preferred first-line strategy, whereas extensively hydrolyzed and amino-acid-based formulas are used when breastfeeding is not feasible or is insufficient. Estimated six-month costs ranged from COP 4,337,640 to COP 14,480,700 (approximately USD 1100–3600), depending on formula type. Conclusions: CMPA requires early recognition, careful clinical evaluation, individualized nutritional management, and improved access to effective and affordable treatment strategies. Full article

Selenium (Se) is an essential trace element. The bioactivity of Se arises from its incorporation into the 21st amino acid, selenocysteine (Sec). Twenty-five human genes have been identified that encode selenoproteins, each of which contains at least one Sec residue. Selenoprotein functions include antioxidant responses, thyroid hormone synthesis, and maintenance of cellular redox homeostasis. Due to its role in critical cellular functions, Se deficiency is associated with morbidities of the cardiovascular system and connective tissue in regions of countries with low soil Se content. While these morbidities are geography-specific and have been mitigated in adults through public health interventions, preterm infants remain susceptible to Se deficiency worldwide. Infants born preterm are deprived of fetal Se accrual in the 3rd trimester of pregnancy, a deficiency compounded by higher Se needs than term infants and older infants and dependence on parenteral nutrition (PN) and fortification. In addition, the composition of selenoproteins and selenometabolites in human milk is different from that in formula and PN, yet little is known about the biological impact of these differences. The knowledge gap in optimal Se supplementation is reflected in discrepant guidelines between North American and European/Chinese nutrition societies, whose recommended Se supplementation in preterm infants differs by more than 2-fold. In this review, we describe the biosynthesis, metabolism, and maternal-fetal transfer of Se. In addition, we address how developmentally regulated aspects of metabolism may impact how preterm infants respond to supplementation with different forms of Se. Lastly, we highlight current challenges and recommendations for optimizing Se levels in neonates based on available data. Full article

Background: Lactopontin (L-OPN) is a pivotal bioactive protein present in breast milk that supports bone development, but its efficacy in a formula matrix is unknown. This study aimed to evaluate the effects of L-OPN-fortified formula on bone growth in a growing rat model and to explore the underlying mechanisms. Methods: Weanling rats (n = 8/group) received daily gavage for four weeks: (1) CON—deionized water; (2) PRO—750 mg/kg·BW mixed protein; or (3) L-OPN—750 mg/kg·BW of the PRO formula fortified with L-OPN. Results: The results showed that the formula fortified with L-OPN could significantly increase bone volume and trabecular bone number (p < 0.05). Furthermore, both femur length and thickness, as well as overall body length, were significantly increased (p < 0.001). In addition, the L-OPN-fortified formula specifically increased the relative abundance of Bacteroides and Parabacteroides in rat feces (p < 0.05). Metabolomic analysis revealed that L-OPN supplementation significantly altered bile acid metabolism, notably increasing serum levels of 12-ketolithocholic acid (12-KLCA), which correlated strongly with bone metrics. Conclusions: These preclinical findings provide a basis for future research in infant formula. Full article

Background: Cow’s milk protein allergy (CMPA) is a common cause of gastrointestinal and dermatologic symptoms in infancy. In clinical practice, infants with atopic dermatitis (AD) and suspected non-IgE-mediated CMPA are frequently managed with formula modification, although real-world comparative data across different formula strategies remain limited. Aim: To evaluate gastrointestinal symptom resolution, improvement in AD, and growth outcomes following formula modification in infants with AD and suspected non-IgE-mediated CMPA. Methods: This retrospective comparative cohort study included 107 infants aged ≤12 months with documented AD and suspected non-IgE-mediated CMPA evaluated at a tertiary academic center between January 2024 and December 2025. Infants were categorized according to initial management strategy: switch to extensively hydrolyzed formula (eHF; n = 63), switch to amino acid formula (AAF; n = 29), or continued standard cow’s milk-based formula (n = 15). The primary outcome was resolution of gastrointestinal symptoms within 2–4 weeks. Secondary outcomes included improvement in AD, weight gain, and need for further formula escalation. Multivariable logistic regression was performed to adjust for potential confounders. Results: Overall, gastrointestinal symptom resolution occurred in 74 of 107 infants (69.2%). Resolution rates were 71.4% in the eHF group, 79.3% in the AAF group, and 40% in the standard formula group (p = 0.01). In adjusted analysis, switching to eHF (aOR 2.8; 95% CI 1.1–7.3; p = 0.03) and AAF (aOR 4.1; 95% CI 1.3–12.5; p = 0.01) was independently associated with higher odds of symptom resolution compared with continued standard formula. Improvement in AD was observed in 57.9% of infants overall and differed significantly across groups (p = 0.04). Mean weight gain during follow-up did not differ significantly between groups (p = 0.63). Subsequent formula escalation was more frequent in the standard formula group (46.7%) compared with eHF (17.5%) and AAF (13.8%) groups (p = 0.004). Conclusions: In infants with AD and suspected non-IgE-mediated CMPA, substitution with extensively hydrolyzed or amino acid formula was independently associated with greater gastrointestinal symptom resolution and improvement in dermatitis compared with continued standard formula, without evidence of compromised growth. These findings provide supportive real-world evidence consistent with current international guidelines; however, given the observational design and potential for residual confounding, they should be interpreted as hypothesis-generating rather than confirmatory evidence of causal treatment effects. Full article

Background/Objectives: Recent studies have shown that the solubilisation of poorly water-soluble drugs can be enhanced by using infant formula as a lipid-based formulation. In those studies, digestion of the triglycerides in infant formula to produce more polar lipids, namely fatty acids and monoglycerides, produced a high-capacity solubilisation environment for weakly basic drugs such as clofazimine, driven mainly by ion-pairing of the fatty acid with the drug. However, digestion of lipid-based formulations is not expected to provide the same effect for nonionised or acidic drugs and in fact may present a reduced solubilisation capacity for weakly acidic drugs. Methods: In this study, a weakly acidic drug, tolfenamic acid, was dispersed in reconstituted infant formula, and the infant formula was digested under in vitro simulated intestinal conditions. The quantity of tolfenamic acid that was solubilised in the infant formula during digestion was determined by high-performance liquid chromatography and small-angle X-ray scattering. Results: Unexpectedly, digestion of the infant formula increased the solubilisation capacity for tolfenamic acid. Reconstituting infant formula at a higher fat content also increased the rate and extent of solubilisation of tolfenamic acid during digestion. The quantity of tolfenamic acid that was solubilised during digestion correlated approximately linearly with the quantity of free fatty acids produced during digestion. Conclusions: These results show that a weakly acidic drug can also exhibit digestion-driven solubilisation in a lipid-based formulation in the absence of ion-pairing and highlights the need to better understand drug response to digestion of lipid-based foods and formulations, and their versatility as a formulation option even for poorly water-soluble acidic drugs. Full article

Cow’s milk allergy (CMA) remains one of the most common food allergies in infancy, requiring the avoidance of cow’s milk and its derivatives. Breast milk is the best source of nutrition for infants. For those infants with CMA whose mothers are unable to breastfeed or choose not to, extensively hydrolysed formulas (eHFs) are widely recommended as first-line milk substitutes, whereas hydrolysed rice formulas (HRFs) are increasingly recognised as a viable alternative. This concept paper provides a healthcare professional (HCP) perspective on HRF, drawing on expert consensus from two meetings convened in 2025. Discussions noted the long history of safe and effective HRF use in Europe, its nutritional adequacy, and the evolving international guidelines supporting HRF as an alternative first-line option. A key meeting outcome was the development of a practical decision tree to help UK clinicians decide when HRF should be the preferred choice. Key considerations for its use in non-breastfed infants include the following: parental/caregiver stress related to persistent symptoms; ongoing symptoms despite multiple interventions; cultural and lifestyle choices; religious dietary requirements; and specialists’ recommendations. Secondary considerations highlighted by HCPs include the following: proven reactions whilst infants are breast-milk-fed together with parental request for formula; faltering growth; multiple symptoms; taste acceptance (older infants); and parental preference based on experience. The role of functional components, such as prebiotics and human milk oligosaccharides (HMOs), was noted in regard to the emerging evidence of benefits to the microbiome and immune development. The experts emphasised the importance of engaging HCPs across all levels of CMA care and addressing challenges in translating current guidance into treatment practice. It was concluded that, overall, HRF represents a nutritionally complete, plant-based alternative that has been shown to be well tolerated (taste, symptoms) in clinical studies. It can be used to broaden therapeutic options for infants with CMA in the UK who are not exclusively fed breast milk. Full article

Cronobacter sakazakii is an opportunistic pathogen commonly associated with powdered infant formula and causes severe neonatal infections. While whole-genome sequencing (WGS)-based single nucleotide polymorphism (SNP) analysis has revolutionized surveillance and outbreak investigations, comprehensive population-level analyses remain limited, and establishing proper thresholds for detecting epidemiologically related C. sakazakii isolates requires assessment using large-scale genomic datasets. We analyzed 1870 C. sakazakii genomes from the United States (1970–2025) to examine pan- and core-genomic structure, analyze SNP distance matrices encompassing 1,747,515 unique pairwise comparisons, and reconstruct population phylogeny. Our analyses revealed exceptional genomic diversity with a large pan-genome of 24,035 gene families and an average of 29,442 ± 13,097 SNPs between genome pairs. Phylogenetic reconstruction identified 22 major clusters encompassing 89.3% of genomes, including environmental complexes demonstrating persistent contamination spanning multiple years. Using 209 monophyletic genome pairs with concordant metadata, we propose a tiered SNP threshold framework (≤234 to 506 SNPs) for detecting potentially epidemiologically-related genomes with improved sensitivity. As genomes from Michigan comprised 39.3% of the dataset, these thresholds should be interpreted with caution when applied to other US regions. This study provides population genomics infrastructure to enhance C. sakazakii surveillance and traceback studies for improving powdered infant formula safety. Full article

The purpose of this study was to examine relationships between infant feeding and parenting self-efficacy. Mothers (N = 121) receiving home visiting reported on PSE and infant feeding at two times (e.g., longitudinally). Mothers were exclusively formula feeding (46.7%), exclusively breastfeeding (19.8%) or combining breastfeeding and formula (33.1%). Infant feeding was regressed on parenting self-efficacy and relevant demographics using logistic regression. Mothers with higher parenting self-efficacy were more likely to be exclusively formula feeding or combination feeding at Time 1. Continued breastfeeding was not predicted by self-efficacy but rather by working status and earlier supplementation. Results suggest higher parenting self-efficacy associated with formula feeding suggests social reinforcement or feelings of success around the enactment of or choice in infant feeding method. Lower parenting self-efficacy associated with initial breastfeeding suggests unsuccessful enactment (i.e., breastfeeding challenges) or negative social reinforcement. More research is needed to understand infant feeding norms and practices in relationship to parenting self-efficacy to best promote breastfeeding intervention and support maternal mental health. Practitioners should work to extend exclusive breastfeeding through supportive positive reinforcement, while limiting formula supplementation. The importance of parental leave for longer breastfeeding duration should be considered when establishing leave policies. Full article

Liquid infant formula has garnered increasing attention due to its mild thermal processing and superior retention of bioactive nutrients. Within such matrices, the lipid source is a critical determinant of protein digestion behavior, yet its influence on peptide bioavailability and intestinal homeostasis remains undefined. Given that efficient peptide absorption is vital for the systemic delivery of bioactivity in infants, understanding the lipid–protein synergy is essential for formula optimization. Moreover, excessive oxidative stress is closely associated with impaired intestinal health and developmental disorders in infants, making the regulation of oxidative stress crucial for maintaining intestinal function. The present study evaluated the effects of three distinct lipid sources—soybean oil (SM), bovine milk fat (BM), and goat milk fat (GM)—on the physicochemical stability, proteolytic digestion, peptide release, intestinal absorption, and oxidative stress modulation of goat-milk-based infant formula. An integrated approach combining physicochemical characterization, in vitro simulated infant digestion, and a Caco-2 intestinal epithelial cell model was employed. we demonstrate that all three lipids (3% w/w) formed stable emulsions with uniform spherical structures and mean particle diameters of 117–300 nm, as visualized by laser confocal microscopy. Following in vitro simulation of infant gastrointestinal digestion, the SM group exhibited the most extensive protein hydrolysis, yielding the highest total peptide content (4.28 ± 0.10 mg/mL) and generated the highest number of peptides identified by LC-MS/MS (474 types). Bioinformatic analysis predicted that peptides from all groups possess potential antihypertensive, hypoglycemic, and immunomodulatory activities. The Caco-2 monolayer cell model demonstrated that although the GM group produced fewer identified peptide species than the SM group (365 types), it achieved significantly higher intestinal peptide absorption rate (55.34 ± 1.05%). Furthermore, the GM digests provided superior protection against H₂O₂-induced oxidative stress in Caco-2 cells, markedly reducing reactive oxygen species levels and suppressing the expression of pro-inflammatory cytokines TNF-α and IL-6. Collectively, these findings reveal that while soybean oil promotes more extensive proteolysis, the use of homologous goat milk lipid enhances peptide bioaccessibility and confers potential cytoprotective effects on intestinal epithelial cells, underscoring its potential as a preferred lipid source in infant formula formulations. Full article

Necrotizing enterocolitis (NEC) is a major cause of illness and death in preterm infants and is increasingly linked to long-term neurodevelopmental issues among survivors. Usually seen as a gastrointestinal disease, NEC is rarely viewed from a brain-centered perspective. In this Perspective, we suggest that NEC should be understood as a disorder of the gut–brain axis affecting neurodevelopment. We combine clinical and experimental evidence showing that intestinal inflammation, microbial imbalance, epithelial barrier failure, and systemic immune activation during NEC all contribute to the disruption of early brain development. We contend that neurodevelopmental damage is a key feature of NEC rather than just a secondary effect of prematurity. Recognizing NEC as a gut–brain axis disorder is crucial for research models, treatment approaches, and assessing long-term outcomes in affected infants. Full article