Search Results (909)

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

The neonatal development period from the time of birth can be considered the period of greatest physiological changes throughout the human lifespan. These changes are partly due to dietary or environmental factors and are also modulated by genetic, neuronal, and humoral influences. The focus of research is increasingly on the microbial colonization of the neonatal intestine, since the establishment of a healthy, symbiotic newborn microbiota not only corresponds closely with nutrient metabolism, immune functions, and growth, but also with the brain as part of the so-called “gut–brain axis”. At the same time, a critical time window of opportunity opens up for the early infant microbiota, which is accessible to modulating approaches in favor of normal infant development. Although the definition of “normal” microbiota in infants still remains challenging, the microbiota of infants delivered at term can be discussed as the gold standard—provided they were exclusively breastfed and have not been exposed to antibiotics. Advances in sequencing technologies now also allow us to identify and characterize the microbiota at the strain level and to provide the scientific rationale for new approaches to modulate the early-life microbiome in a more targeted and personalized way—applicable also for formula-fed children who cannot be supplied with human milk. This review addresses the challenges associated with the “healthy” development of a newborn during the first weeks and months of life and discusses potentially modifiable external factors in light of the requirements for the establishment of a functional gut microbiota, gastrointestinal system, and gut–brain axis. Full article

Early life represents a critical developmental programming window during which nutrition and microbial exposures shape long-term physiological function. Feeding mode is a major determinant of infant gut microbiota assembly and metabolic activity. This narrative review synthesizes current evidence comparing breastfeeding (BF) and formula feeding in relation to microbial composition, functional capacity, and immune programming during the preweaning and early postweaning periods. BF may support a relatively stable, bifidobacteria-dominated microbiota enriched in pathways involved in carbohydrate utilization, vitamin biosynthesis, and immune modulation. Human milk oligosaccharides, secretory IgA, lactoferrin, and milk-associated microbes collectively guide microbial succession, enhance barrier integrity, and support immune tolerance. In contrast, formula-fed infants typically exhibit greater microbial diversity, earlier transition toward adult-like profiles, and increased abundance of facultative anaerobes, alongside the enrichment of pathways related to bile acid and amino acid metabolism. Microbiota patterns in formula-fed infants are further influenced by formula composition, including protein load, lipid structure, and supplementation with prebiotics, probiotics, and human milk oligosaccharide analogues. Although advances in formula design have reduced compositional gaps, functional differences in microbial stability and immune programming persist. Recognizing early infancy as a sensitive programming window underscores the need for microbiome-informed nutritional strategies and longitudinal, multi-omics research to clarify causal mechanisms and optimize early-life interventions. Full article

Background: Current recommendations for infant weaning suggest the early introduction of solid and diverse foods. Although homemade meals are advisable, there is a demand for commercially available complementary foods (CACFs), and the information present on their labeling influences caregivers’ choices. The aim of this study was to evaluate recommended-age-of-introduction labeling of CACFs in the Portuguese market, in light of current guidelines for complementary feeding. Methods: Between November and December 2025, labels of all CACFs found in infant feeding sections of 13 Portuguese grocery retailers were analyzed. Milk formulas, powders, products for children over 15 months, and those for children with food allergies or intolerances were excluded. Results: Of the 539 products analyzed, 458 showed a recommended age for introduction, ranging from 4 to 12 months, with significant variability being observed between food categories. Significant variability was also observed in the recommended age for introduction depending on whether major allergens were present. Conclusions: The results of our study identified an age-segmented approach to complementary feeding recommendations in CACF labeling, not reflecting current infant feeding guidelines that support complementary feeding. Our results reinforce the need for more support from scientific evidence and health guidelines in food availability and marketing. Full article

Cronobacter spp. is a pathogenic genus comprising seven species, of which C. sakazakii is particularly notable for its association with neonatal outbreaks linked to powdered infant formula. The severity of infections is associated with virulence factors (VFs) and β-lactam antibiotic resistance genes (ARGs). Next-generation sequencing (NGS) has enabled precise strain typing through core genome multilocus sequence typing (cgMLST), enhancing discrimination and accuracy. This study aimed to use cgMLST (2831 genes) to genomically characterize 34 Cronobacter strains which had been isolated from powdered milk and production surfaces between 2011 and 2022. The identified strains included C. sakazakii ST1, ST4, ST13, ST31 and ST83, as well as C. malonaticus ST60. Overall, there were eight clusters of closely related strains. All strains exhibited resistance to cephalothin, 18 were resistant to ceftazidime and 11 to ampicillin. Various resistance genes (bla_CSA, bla_CMA, fos, qacJ, marA, AcrAB-TolC, and mcr-9.1) and virulence genes (cpa, nanAKT, fic, relB, fliC) were detected, with some genes being exclusive to C. sakazakii. All strains carried plasmids and mobile genetic elements. The multidrug resistance and presence of virulence genes in these isolates highlight the significant risk that C. sakazakii-contaminated powdered dairy products pose to public health, underscoring the need to adopt proper hygienic manufacturing practices and effectively implement HACCP in their production. Full article