Nursing â€ș Nutrition and Dietetics

Infant Nutrition and Health

Description

This cluster of papers focuses on the composition and health effects of human milk, particularly in relation to preterm infants. It covers topics such as the composition of human milk, the impact on growth outcomes and neurodevelopment, the role in preventing necrotizing enterocolitis, the significance of oligosaccharides and lactoferrin, the development of intestinal microbiota, and the use of probiotics. The papers also discuss the nutritional and immune developmental significance of human milk for preterm infants.

Keywords

Human Milk Composition; Preterm Infants; Necrotizing Enterocolitis; Oligosaccharides; Lactoferrin; Growth Outcomes; Microbiota Development; Probiotics; Nutritional Significance; Immune Development

Whether early diet influences long-term health or achievement is a key question in nutrition. Such long-term consequences would invoke the concept of 'programming'--a more general process whereby a stimulus or 
 Whether early diet influences long-term health or achievement is a key question in nutrition. Such long-term consequences would invoke the concept of 'programming'--a more general process whereby a stimulus or insult at a critical period of development has lasting or lifelong significance. Data from small mammals and primates show that early nutrition may have potentially important long-term effects, for example on blood lipids, plasma insulin, obesity, atherosclerosis, behaviour and learning. Corresponding studies in man have been largely retrospective and difficult to interpret. The preterm infant is however an important model for human research because formal random assignment to early diet is practical. A large prospective randomized multicentre study has been undertaken on 926 preterm infants to test the hypothesis that early diet influences long-term outcome. Diets included human milk, standard formula and nutrient-enriched preterm formula. The diet consumed for on average the first month post partum had a major impact on subsequent developmental attainment, growth and allergic status in early childhood. That such a brief period of dietary manipulation has lasting significance implies that the neonatal period is critical for nutrition after preterm birth. These data may have broader implications for human nutrition.
Research on human milk oligosaccharides (HMOs) has received much attention in recent years. However, it started about a century ago with the observation that oligosaccharides might be growth factors for 
 Research on human milk oligosaccharides (HMOs) has received much attention in recent years. However, it started about a century ago with the observation that oligosaccharides might be growth factors for a so-called bifidus flora in breast-fed infants and extends to the recent finding of cell adhesion molecules in human milk. The latter are involved in inflammatory events recognizing carbohydrate sequences that also can be found in human milk. The similarities between epithelial cell surface carbohydrates and oligosaccharides in human milk strengthen the idea that specific interactions of those oligosaccharides with pathogenic microorganisms do occur preventing the attachment of microbes to epithelial cells. HMOs may act as soluble receptors for different pathogens, thus increasing the resistance of breast-fed infants. However, we need to know more about the metabolism of oligosaccharides in the gastrointestinal tract. How far are oligosaccharides degraded by intestinal enzymes and does oligosaccharide processing (e.g. degradation, synthesis, and elongation of core structures) occur in intestinal epithelial cells? Further research on HMOs is certainly needed to increase our knowledge of infant nutrition as it is affected by complex oligosaccharides.
ABSTRACT An essential feature of mammary gland differentiation during pregnancy is the formation of alveoli composed of polarized epithelial cells, which, under the influence of lactogenic hormones, secrete vectorially and 
 ABSTRACT An essential feature of mammary gland differentiation during pregnancy is the formation of alveoli composed of polarized epithelial cells, which, under the influence of lactogenic hormones, secrete vectorially and sequester milk proteins. Previous culture studies have described either organization of cells polarized towards lumina containing little or no demonstrable tissue-specific protein, or establishment of functional secretory cells exhibiting little or no glandular architecture. In this paper, we report that tissue-specific vectorial secretion coincides with the formation of functional alveoli-like structures by primary mammary epithelial cells cultured on a reconstituted basement membrane matrix (derived from Engelbreth-Holm-Swarm murine tumour). Morphogenesis of these unique three-dimensional structures was initiated by cell-directed remodelling of the exogenous matrix leading to reorganization of cells into matrix-ensheathed aggregates by 24 h after plating. The aggregates subsequently cavitated, so that by day 6 the cells were organized into hollow spheres in which apical cell surfaces faced lumina sealed by tight junctions and basal surfaces were surrounded by a distinct basal lamina. The profiles of proteins secreted into the apical (luminal) and basal (medium) compartments indicated that these alveoli-like structures were capable of an appreciable amount of vectorial secretion. Immunoprecipitation with a broad spectrum milk antiserum showed that more than 80% of caseins were secreted into the lumina, whereas iron-binding proteins (both lactoferrin and transferrin) were present in comparable amounts in each compartment. Thus, these mammary cells established protein targeting pathways directing milk-specific proteins to the luminal compartment. A time course monitoring secretory activity demonstrated that establishment of tissue-specific vectorial secretion and increased total and milk protein secretion coincided with functional alveolar-like multicellular architecture. This culture system is unique among models of epithelial cell polarity in that it demonstrates several aspects of epithelial cell polarization: vectorial secretion, apical junctions, a sequestered compartment and formation of a basal lamina. These lumina-containing structures therefore reproduce the dual role of mammary epithelia to secrete vectorially and to sequester milk proteins. Thus, in addition to maintaining tissue-specific cytodifferentiation and function, a basement membrane promotes the expression of tissue-like morphogenesis.
To determine the effect of a human Lactobacillus strain (Lactobacillus casei sp strain GG, Gefilac) on recovery from acute diarrhea (82% rotavirus), 71 well-nourished children between 4 and 45 months 
 To determine the effect of a human Lactobacillus strain (Lactobacillus casei sp strain GG, Gefilac) on recovery from acute diarrhea (82% rotavirus), 71 well-nourished children between 4 and 45 months of age were studied. After oral rehydration, the patients randomly received either Lactobacillus GG-fermented milk product, 125 g (10(10-11) colony-forming units) twice daily (group 1); Lactobacillus GG freeze-dried powder, one dose (10(10-11) colony-forming units) twice daily (group 2); or a placebo, a pasteurized yogurt (group 3) 125 g twice daily; each diet was given for 5 days, in addition to normal full diet otherwise free of fermented dairy products. The mean (SD) duration of diarrhea after commencing the therapy was significantly shorter in group 1 (1.4 [0.8] days) and in group 2 (1.4 [0.8] days) than in group 3 (2.4 [1.1] days); F = 8.70, P less than 0.001. After rehydration, each dietary group maintained a positive weight trend. The urinary lactulose-mannitol recovery ratios (means [95% confidence intervals]) on admission were 0.09 (0.03, 0.24) in group 1, 0.12 (0.07, 0.22) in group 2, and 0.08 (0.04, 0.18) in group 3; no significant alterations in intestinal permeability were observed at retesting after 2 days of realimentation. The result indicates that early nutritional repletion after rehydration causes no mucosal disruption and is beneficial for recovery from diarrhea. It is further suggested that Lactobacillus GG in the form of fermented milk or freeze-dried powder is effective in shortening the course of acute diarrhea.
Lactoferrin, an iron-binding protein previously shown to occur in many external secretions, is identified as one of the major proteins present in human and guinea pig neutrophilic polymorphonuclear leukocytes. The 
 Lactoferrin, an iron-binding protein previously shown to occur in many external secretions, is identified as one of the major proteins present in human and guinea pig neutrophilic polymorphonuclear leukocytes. The identification of this protein in leukocyte extracts was based upon a comparison of its electrophoretic, antigenic, and iron-combining properties with the corresponding properties of the same protein isolated from human and guinea pig milk. Immunochemical quantitations showed that lactoferrin occurs in human neutrophilic leukocytes at the concentration of 3 microg per 10(6) cells. Tissue cultures from guinea pig bone marrow and spleen actively synthesized the protein, as shown both by net production of lactoferrin and incorporation of labeled amino acids into the protein. Immunohistochemical data indicate that lactoferrin first appears in myeloid cells at the stage of the promyelocyte.
Streptococcus mutans and Vibrio cholerae , but not Escherichia coli , were killed by incubation with purified human apolactoferrin. Concentrations of lactoferrin below that necessary for total inhibition resulted in 
 Streptococcus mutans and Vibrio cholerae , but not Escherichia coli , were killed by incubation with purified human apolactoferrin. Concentrations of lactoferrin below that necessary for total inhibition resulted in a marked reduction in viable colony-forming units. This bactericidal effect was contingent upon the metal-chelating properties of the lactoferrin molecule.
A method of clinical staging for infants with necrotizing enterocolitis (NEC) is proposed. On the basis of assigned stage at the time of diagnosis, 48 infants were treated with graded 
 A method of clinical staging for infants with necrotizing enterocolitis (NEC) is proposed. On the basis of assigned stage at the time of diagnosis, 48 infants were treated with graded intervention. For Stage I infants, vigorous diagnostic and supportive measures are appropriate. Stage II infants are treated medically, including parenteral and gavage aminoglycoside antibiotic, and Stage III patients require operation. All Stage I patients survived, and 32 of 38 Stage II and III patients (85%) survived the acute episode of NEC. Bacteriologic evaluation of the gastrointestinal microflora in these neonates has revealed a wide range of enteric organisms including anaerobes. Enteric organisms were cultured from the blood of four infants dying of NEC. Sequential cultures of enteric organisms reveal an alteration of flora during gavage antibiotic therapy. These studies support the use of combination antimicrobial therapy in the treatment of infants with NEC.
Acute diarrhoea is a serious cause of infant morbidity and mortality, and the development of preventive measures remains an important goal. Bifidobacteria (which constitute the predominant intestinal flora of breastfed 
 Acute diarrhoea is a serious cause of infant morbidity and mortality, and the development of preventive measures remains an important goal. Bifidobacteria (which constitute the predominant intestinal flora of breastfed infants), as well as other lactic-acid-producing organisms such as Streptococcus thermophilus, are thought to have a protective effect against acute diarrhoeal disease. However, their efficacy has not been assessed in controlled trials. In a double-blind, placebo-controlled trial, infants aged 5-24 months who were admitted to a chronic medical care hospital were randomised to receive a standard infant formula or the same formula supplemented with Bifidobacterium bifidum and S thermophilus. Patients were evaluated daily for occurrence of diarrhoea, and faecal samples, obtained weekly, were analysed for rotavirus antigen by enzyme immunoassay. Faecal samples were also obtained during an episode of diarrhoea for virological and bacteriological analyses. 55 subjects were evaluated for a total of 4447 patient-days during 17 months. 8 (31%) of the 26 patients who received the control formula and 2 (7%) of 29 who received the supplemented formula developed diarrhoea during the course of the study (p = 0.035, Fisher's exact test, two-tailed). 10 (39%) of the subjects who received the control formula and 3 (10%) of those who received the supplemented formula shed rotavirus at some time during the study (p = 0.025). The supplementation of infant formula with B bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding in infants admitted to hospital.
The neonatal intestinal microbiota is a complex ecosystem composed of numerous genera, species and strains of bacteria. This enormous cell mass performs a variety of unique activities that affect both 
 The neonatal intestinal microbiota is a complex ecosystem composed of numerous genera, species and strains of bacteria. This enormous cell mass performs a variety of unique activities that affect both the colonic and systemic physiology. Its primary activities include nutritive, metabolic, immunological and protective functions. Most studies of infants have been based on faecal samples using the classical plating techniques with culturing on specific media. The limitations of these methods must be taken into account when evaluating the varying results of the different studies. The establishment of the gut microbial population is not strictly a succession in the ecological sense; it is rather a complex process influenced by microbial and host interactions and by external and internal factors. The climax intestinal flora is attained in successive stages. The foetal intestine is sterile and bathed in swallowed amniotic fluid. Following delivery, multiple different antigens challenge the intestine of the newborn. The maternal intestinal flora is a source of bacteria for the neonatal gut. The bacterial flora is usually heterogeneous during the first few days of life, independently of feeding habits. After the first week of life, a stable bacterial flora is usually established. In full-term infants a diet of breast milk induces the development of a flora rich in Bifidobacterium spp. Other obligate anaerobes, such as Clostridium spp. and Bacteroides spp., are more rarely isolated and also enterobacteria and enterococci are relatively few. During the corresponding period, formula-fed babies are often colonized by other anaerobes in addition to bifidobacteria and by facultatively anaerobic bacteria; the development of a "bifidus flora" is unusual. In other studies the presence of a consistent number of bifidobacteria in infants delivered in large urban hospitals has not been demonstrated, whether the babies were bottle fed or exclusively breastfed. The predominant faecal bacteria were coliforms and bacteroides. According to these studies, environmental factors may be more important than breastfeeding in gut colonization after delivery. Environmental factors are indeed extremely important for the intestinal colonization of infants born by caesarean section. In these infants, the establishment of a stable flora characterized by a low incidence of Bacteroides spp. and by the isolation of few other bacteria is consistently delayed. In extremely low-birthweight infants, hospitalization in neonatal intensive care units, characterized by prolonged antibiotic therapy, parenteral nutrition, delayed oral feedings and intubation seems to affect the composition of the intestinal microbiota. The gut is colonized by a small number of bacterial species; Lactobacillus and Bifidobacteria spp. are seldom, if ever, identified. According to the few studies so far performed, the predominant species are Enterococcus faecalis, E. coli, Enterobacter cloacae, Klebsiella pneumoniae, Staphylococcus epidermidis and Staphylococcus haemolyticus. Hygienic conditions and antimicrobial procedures strongly influence the intestinal colonization pattern.
Recent investigations have demonstrated that human milk contains a variety of bacterial genera; however, as of yet very little work has been done to characterize the full diversity of these 
 Recent investigations have demonstrated that human milk contains a variety of bacterial genera; however, as of yet very little work has been done to characterize the full diversity of these milk bacterial communities and their relative stability over time. To more thoroughly investigate the human milk microbiome, we utilized microbial identification techniques based on pyrosequencing of the 16S ribosomal RNA gene. Specifically, we characterized the bacterial communities present in milk samples collected from 16 women at three time-points over four weeks. Results indicated that milk bacterial communities were generally complex; several genera represented greater than 5% of the relative community abundance, and the community was often, yet not always, stable over time within an individual. These results support the conclusion that human milk, which is recommended as the optimal nutrition source for almost all healthy infants, contains a collection of bacteria more diverse than previously reported. This finding begs the question as to what role this community plays in colonization of the infant gastrointestinal tract and maintaining mammary health.
Although lactoferrin has antimicrobial activity, its mechanism of action is not full defined. Recently we have shown that the protein alters the Gram-negative outer membrane. As this membrane protects Gram-negative 
 Although lactoferrin has antimicrobial activity, its mechanism of action is not full defined. Recently we have shown that the protein alters the Gram-negative outer membrane. As this membrane protects Gram-negative cells from lysozyme, we have studied whether lactoferrin's membrane effect could enhance the antibacterial activity of lysozyme. We have found that while each protein alone is bacteriostatic, together they can be bactericidal for strains of V. cholerae, S. typhimurium, and E. coli. The bactericidal effect is dose dependent, blocked by iron saturation of lactoferrin, and inhibited by high calcium levels, although lactoferrin does not chelate calcium. Using differing media, the effect of lactoferrin and lysozyme can be partially or completely inhibited; the degree of inhibition correlating with media osmolarity. Transmission electron microscopy shows that E. coli cells exposed to lactoferrin and lysozyme at 40 mOsm become enlarged and hypodense, suggesting killing through osmotic damage. Dialysis chamber studies indicate that bacterial killing requires direct contact with lactoferrin, and work with purified LPS suggests that this relates to direct LPS-binding by the protein. As lactoferrin and lysozyme are present together in high levels in mucosal secretions and neutrophil granules, it is probable that their interaction contributes to host defense.
Human milk contains large quantities of iron-binding protein, of which the greater proportion is lactoferrin, though small amounts of transferrin are also present. Three samples of human milk with unsaturated 
 Human milk contains large quantities of iron-binding protein, of which the greater proportion is lactoferrin, though small amounts of transferrin are also present. Three samples of human milk with unsaturated iron-binding capacities of between 56 and 89% had a powerful bacteriostatic effect on <i>Escherichia coli</i> O111/B4. The bacteriostatic properties of milk were abolished if the iron-binding proteins were saturated with iron. Purified human lactoferrin, in combination with specific <i>E. coli</i> antibody, strongly inhibited the growth of <i>E. coli</i>, and this effect was also abolished by saturating the lactoferrin with iron. Guinea-pig milk also contains lactoferrin and transferrin. Newly born guinea-pigs fed on an artificial diet and dosed with <i>E. coli</i> O111 had higher counts of <i>E. coli</i> O111 in the intestine than suckled animals. The apparent suppressive effect of guinea-pig milk on <i>E. coli</i> in the intestine could be reversed by feeding the iron compound haematin. It seems that iron-binding proteins in milk may play an important part in resistance to infantile enteritis caused by <i>E. coli</i>.
Nutrient intakes meeting recommended dietary intakes (RDIs) take time to establish and once established are rarely maintained throughout hospital stay in preterm infants. A nutrient deficit, therefore, accrues. RDI are 
 Nutrient intakes meeting recommended dietary intakes (RDIs) take time to establish and once established are rarely maintained throughout hospital stay in preterm infants. A nutrient deficit, therefore, accrues. RDI are based on needs for maintenance and growth, with no provision to replace this deficit. We, therefore, hypothesized that postnatal malnutrition and growth retardation were inevitable in infants fed current RDI.Dietary intakes were prospectively collected, by a single observer (N.P.), on a daily basis in a group of preterm infants (n = 105; birth weight </=1750 g; gestational age </=34 weeks) admitted to neonatal intensive care unit over a 6-month period. Actual was subtracted from recommended energy (120 kcal/kg/day) and protein (3 g/kg/day) intakes and nutritional deficits calculated. Infants were weighed on admission and throughout hospital stay. The data were analyzed using a combination of repeated measures analysis of variance and stepwise regression analysis.Nutrient intakes meeting current RDIs were rarely achieved during early life. By the end of the first week, cumulative energy and protein deficits were 406 +/- 92 and 335 +/- 86 kcal/kg and 14 +/- 3 and 12 +/- 4 g/kg in infants </=30 and those at >/=31 weeks. By the end of the fifth week, cumulative energy and protein deficits were 813 +/- 542 and 382 +/- 263 kcal/kg and 23 +/- 12 and 13 +/- 15 g/kg and the z scores were -1.14 +/-.6 and -.82 +/-.5 for infants at </=30 and >/=31 weeks. Stepwise regression analysis indicated that variation in dietary intake accounted for 45% of the variation in changes in z score.Preterm infants inevitably accumulate a significant nutrient deficit in the first few weeks of life that will not be replaced when current RDIs are fed. This deficit can be directly related to subsequent postnatal growth retardation.postnatal growth retardation, preterm infants.
ABSTRACT The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth 
 ABSTRACT The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480 ), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines , 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable‐growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.
Objective. We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. Patients and Methods. A prospective, masked, 
 Objective. We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. Patients and Methods. A prospective, masked, randomized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW (&amp;lt;1500 g) infants. VLBW infants who started to fed enterally and survived beyond the seventh day after birth were eligible for the trial. They were randomized into 2 groups after parental informed consents were obtained. The infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) with breast milk twice daily until discharged. Infants in the control group were fed with breast milk alone. The clinicians caring for the infants were blinded to the group assignment. The primary outcome was death or NEC (≄ stage 2). Results. Three hundred sixty-seven infants were enrolled: 180 in the study group and 187 in the control group. The demographic and clinical variables were similar in both groups. The incidence of death or NEC (≄ stage 2) was significantly lower in the study group (9 of 180 vs 24 of 187). The incidence of NEC (≄ stage 2) was also significantly lower in the study when compared with the control group (2 of 180 vs 10 of 187). There were 6 cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood culture grew Lactobacillus or Bifidobacterium species. Conclusion. Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants.
The Babson and Benda 1976 "fetal-infant growth graph" for preterm infants is commonly used in neonatal intensive care. Its limits include the small sample size which provides low confidence in 
 The Babson and Benda 1976 "fetal-infant growth graph" for preterm infants is commonly used in neonatal intensive care. Its limits include the small sample size which provides low confidence in the extremes of the data, the 26 weeks start and the 500 gram graph increments. The purpose of this study was to develop an updated growth chart beginning at 22 weeks based on a meta-analysis of published reference studies.
Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears. It consists of a single-chain polypeptide with two 
 Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears. It consists of a single-chain polypeptide with two gobular lobes and is relatively resistant to proteolysis. The complete cDNAs for lactoferrin from human milk, neutrophils, and bovine milk have been reported, and recombinant proteins have been produced. Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria. Its presence in neutrophils and its release during inflammation suggest that lactoferrin is also involved in phagocytic killing and immune responses. Additionally, lactoferrin may function in ways not related to iron-binding, e.g. as a growth factor and as a bactericidal agent. This review attempts to evaluate these proposed functions and their biological significance in more detail.
The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth 
 The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth Standard, b) smooth the data between the preterm and WHO estimates, informed by the Preterm Multicentre Growth (PreM Growth) study while maintaining data integrity from 22 to 36 and at 50 weeks, and to c) re-scale the chart x-axis to actual age (rather than completed weeks) to support growth monitoring. Systematic review, meta-analysis, and growth chart development. We systematically searched published and unpublished literature to find population-based preterm size at birth measurement (weight, length, and/or head circumference) references, from developed countries with: Corrected gestational ages through infant assessment and/or statistical correction; Data percentiles as low as 24 weeks gestational age or lower; Sample with greater than 500 infants less than 30 weeks. Growth curves for males and females were produced using cubic splines to 50 weeks post menstrual age. LMS parameters (skew, median, and standard deviation) were calculated. Six large population-based surveys of size at preterm birth representing 3,986,456 births (34,639 births < 30 weeks) from countries Germany, United States, Italy, Australia, Scotland, and Canada were combined in meta-analyses. Smooth growth chart curves were developed, while ensuring close agreement with the data between 24 and 36 weeks and at 50 weeks. The revised sex-specific actual-age growth charts are based on the recommended growth goal for preterm infants, the fetus, followed by the term infant. These preterm growth charts, with the disjunction between these datasets smoothing informed by the international PreM Growth study, may support an improved transition of preterm infant growth monitoring to the WHO growth charts.
Breastfed infants have lower morbidity and mortality due to diarrhea than those fed artificially. This had been attributed primarily to the secretory antibodies and prebiotic factors in human milk. Oligosaccharides 
 Breastfed infants have lower morbidity and mortality due to diarrhea than those fed artificially. This had been attributed primarily to the secretory antibodies and prebiotic factors in human milk. Oligosaccharides are the third largest component of human milk. They were initially considered to be functionless by-products of glycoprotein and glycolipid synthesis during milk production. However, in the past few decades it has become apparent that the human milk oligosaccharides are composed of thousands of components, at least some of which protect against pathogens. Oligosaccharide protection against infectious agents may result in part from their prebiotic characteristics, but is thought to be primarily due to their inhibition of pathogen binding to host cell ligands. Most human milk oligosaccharides are fucosylated, and their production depends on enzymes encoded by the genes associated with expression of the Lewis blood group system. The expression of specific fucosylated oligosaccharides in milk thus varies in relation to maternal Lewis blood group type, and is significantly associated with the risk of infectious disease in breastfed infants. Specific fucosylated moieties of oligosaccharides and related glycoconjugates (glycans) are able to inhibit binding and disease by specific pathogens. This review presents the argument that specific glycans, especially the oligosaccharides, are the major constituent of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. The large input of energy expended by the mother in the synthesis of milk oligosaccharides is consistent with the human reproductive strategy of large parental input into rearing relatively few offspring through a prolonged period of maturation. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit diseases caused by mucosal pathogens.
Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that are highly abundant in and unique to human milk. Originally, HMOs were discovered as a prebiotic "bifidus 
 Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that are highly abundant in and unique to human milk. Originally, HMOs were discovered as a prebiotic "bifidus factor" that serves as a metabolic substrate for desired bacteria and shapes an intestinal microbiota composition with health benefits for the breast-fed neonate. Today, HMOs are known to be more than just "food for bugs". An accumulating body of evidence suggests that HMOs are antiadhesive antimicrobials that serve as soluble decoy receptors, prevent pathogen attachment to infant mucosal surfaces and lower the risk for viral, bacterial and protozoan parasite infections. In addition, HMOs may modulate epithelial and immune cell responses, reduce excessive mucosal leukocyte infiltration and activation, lower the risk for necrotizing enterocolitis and provide the infant with sialic acid as a potentially essential nutrient for brain development and cognition. Most data, however, stem from in vitro, ex vivo or animal studies and occasionally from association studies in mother–infant cohorts. Powered, randomized and controlled intervention studies will be needed to confirm relevance for human neonates. The first part of this review introduces the pioneers in HMO research, outlines HMO structural diversity and describes what is known about HMO biosynthesis in the mother's mammary gland and their metabolism in the breast-fed infant. The second part highlights the postulated beneficial effects of HMO for the breast-fed neonate, compares HMOs with oligosaccharides in the milk of other mammals and in infant formula and summarizes the current roadblocks and future opportunities for HMO research.
Lactoferrin is a 703-amino acid glycoprotein originally isolated from milk. Plasma lactoferrin is predominantly neutrophil derived but indications are that it may also be produced by other cells. Lactoferrin in 
 Lactoferrin is a 703-amino acid glycoprotein originally isolated from milk. Plasma lactoferrin is predominantly neutrophil derived but indications are that it may also be produced by other cells. Lactoferrin in body fluids is found in the iron-free form, the monoferric form and in the diferric form. Three isoforms of lactoferrin have been isolated, ie two with RNase activity (lactoferrin-beta and lactoferrin-gamma) and one without RNase activity (lactoferrin-alpha). Receptors for lactoferrin can be found on intestinal tissue, monocytes/macrophages, neutrophils, lymphocytes, platelets, and on certain bacteria. A wide spectrum of functions are ascribed to lactoferrin. These range from a role in the control of iron availability to immune modulation. More research is necessary however to obtain clarity with regard to the exact mechanism of action of lactoferrin.
Background. In a large-scale study of feeding strategies in premature infants (early vs later initiation of enteral feeding, continuous vs bolus tube-feeding, and human milk vs formula), the feeding of 
 Background. In a large-scale study of feeding strategies in premature infants (early vs later initiation of enteral feeding, continuous vs bolus tube-feeding, and human milk vs formula), the feeding of human milk had more effect on the outcomes measured than any other strategy studied. Therefore, this report describes the growth, nutritional status, feeding tolerance, and health of participating premature infants who were fed fortified human milk (FHM) in comparison with those who were fed exclusively preterm formula (PF). Methods. Premature infants were assigned randomly in a balanced two-way design to early (gastrointestinal priming for 10 days) versus late initiation of feeding (total parenteral nutrition only) and continuous infusion versus intermittent bolus tube-feeding groups. The type of milk was determined by parental choice and infants to receive their mother's milk were randomized separately from those to receive formula. The duration of the study spanned the entire hospitalization of the infant. To evaluate human milk versus formula feeding, we compared outcomes of infants fed &amp;gt;50 mL · kg−1 · day−1 of any human milk (averaged throughout the hospitalization) with those of infants fed exclusively PF. Growth, feeding tolerance, and health status were measured daily. Serum indices of nutritional status were measured serially, and 72-hour nutrient balance studies were conducted at 6 and 9 weeks postnatally. Results. A total of 108 infants were fed either &amp;gt;50 mL · kg−1 · day−1 human milk (FHM,n = 62) or exclusively PF (n = 46). Gestational age (28 ± 1 weeks each), birth weight (1.07 ± 0.17 vs 1.04 ± 0.19 kg), birth length and head circumference, and distribution among feeding strategies were similar between groups. Infants fed FHM were discharged earlier (73 ± 19 vs 88 ± 47 days) despite significantly slower rates of weight gain (22 ± 7 vs 26 ± 6 g · kg−1 · day−1), length increment (0.8 ± 0.3 vs 1.0 ± 0.3 cm · week−1), and increment in the sum of five skinfold measurements (0.86 ± 0.40 vs 1.23 ± 0.42 mm · week−1) than infants fed PF. The incidence of necrotizing enterocolitis and late-onset sepsis was less in the FHM group. Overall, there were no differences in any measure of feeding tolerance between groups. Milk intakes of infants fed FHM were significantly greater than those fed PF (180 ± 13 vs 157 ± 10 mL · kg−1 · day−1). The intakes of nitrogen and copper were higher and magnesium and zinc were lower in group FHM versus PF. Fat and energy absorption were lower and phosphorus, zinc, and copper absorption were higher in group FHM versus PF. The postnatal retention (balance) surpassed the intrauterine accretion rate of nitrogen, phosphorus, magnesium, zinc, and copper in the FHM group, and of nitrogen, magnesium, and copper in the PF group. Conclusions. Although the study does not allow a comparison of FHM with unfortified human milk, the data suggest that the unique properties of human milk promote an improved host defense and gastrointestinal function compared with the feeding of formula. The benefits of improved health (less sepsis and necrotizing enterocolitis) associated with the feeding of FHM outweighed the slower rate of growth observed, suggesting that the feeding of FHM should be promoted actively in premature infants.
An obvious difference between breast-fed and formula-fed newborn infants is the development of the intestinal flora, considered to be of importance for protection against harmful micro-organisms and for the maturation 
 An obvious difference between breast-fed and formula-fed newborn infants is the development of the intestinal flora, considered to be of importance for protection against harmful micro-organisms and for the maturation of the intestinal immune system. In this study, novel molecular identification methods were used to verify the data obtained by traditional culture methods and to validate the culture independent fluorescent in situ hybridization (FISH) technique.From each of six breast-fed and six formula-fed newborn infants, six fecal samples were obtained during the first 20 days of life. The microbial compositions of the samples were analyzed by culturing on specific media and by FISH, by using specific 16S rRNA-targeted oligonucleotide probes. The colonies growing on the media were identified by random amplified polymorphic DNA pattern analysis and by polymerase chain reaction amplification and subsequent analysis of the 16S rRNA gene.Molecular identification of the colonies showed that the selective media are insufficiently selective and unsuitable for quantitative analyses. Qualitative information from the culturing results combined with the data obtained by the FISH technique revealed initial colonization in all infants of a complex (adult-like) flora. After this initial colonization, a selection of bacterial strains began in all infants, in which Bifidobacterium strains played an important role. In all breast-fed infants, bifidobacteria become dominant, whereas in most formula-fed infants similar amounts of Bacteroides and bifidobacteria (approximately 40%) were found. The minor components of the fecal samples from breast-fed infants were mainly lactobacilli and streptococci; samples from formula-fed infants often contained staphylococci, Escherichia coli, and clostridia.This study confirms the differences in development of intestinal flora between breast-fed and formula-fed infants. The results obtained from the FISH technique were consistent. Although the repertoire of probes for this study was not yet complete, the FISH technique will probably become the method of reference for future studies designed to develop breast-fed-like intestinal flora in formula-fed infants.
This report presents the revised growth charts for the United States. It summarizes the history of the 1977 National Center for Health Statistics (NCHS) growth charts, reasons for the revision, 
 This report presents the revised growth charts for the United States. It summarizes the history of the 1977 National Center for Health Statistics (NCHS) growth charts, reasons for the revision, data sources and statistical procedures used, and major features of the revised charts.Data from five national health examination surveys collected from 1963 to 1994 and five supplementary data sources were combined to establish an analytic growth chart data set. A variety of statistical procedures were used to produce smoothed percentile curves for infants (from birth to 36 months) and older children (from 2 to 20 years), using a two-stage approach. Initial curve smoothing for selected major percentiles was accomplished with various parametric and nonparametric procedures. In the second stage, a normalization procedure was used to generate z-scores that closely match the smoothed percentile curves.The 14 NCHS growth charts were revised and new body mass index-for-age (BMI-for-age) charts were created for boys and girls (http://www.cdc.gov/growthcharts). The growth percentile curves for infants and children are based primarily on national survey data. Use of national data ensures a smooth transition from the charts for infants to those for older children. These data better represent the racial/ethnic diversity and the size and growth patterns of combined breast- and formula-fed infants in the United States. New features include addition of the 3rd and 97th percentiles for all charts and extension of all charts for children and adolescents to age 20 years.Created with improved data and statistical curve smoothing procedures, the United States growth charts represent an enhanced instrument to evaluate the size and growth of infants and children.
SummaryAn improved method has been developed for assay of muramidase in several biological systems. This method involves measurement of the rate of lysis of a 25 mg% suspension of M. 
 SummaryAn improved method has been developed for assay of muramidase in several biological systems. This method involves measurement of the rate of lysis of a 25 mg% suspension of M. lysodeikticus in 0.05 M NaCl and M/15 phosphate buffer, pH 6.2. The rate of lysis is measured in a Beckman DB spectrophotometer at 540 mΌ with an attached recorder. This modification allows continuous measurement of the initial reaction velocity for samples containing from 0.1 to 10 Όg of muramidase.
Background: Newborn infants in modern maternity hospitals are subject to numerous factors that affect normal intestinal colonization-for example, cesarean delivery and antimicrobial agents. To study the duration of the effect 
 Background: Newborn infants in modern maternity hospitals are subject to numerous factors that affect normal intestinal colonization-for example, cesarean delivery and antimicrobial agents. To study the duration of the effect of external factors on intestinal colonization, two groups of infants with different delivery methods were investigated. Methods: The fecal flora of 64 healthy infants was studied prospectively. Thirty-four infants were delivered vaginally, and 30 by cesarean birth with antibiotic prophylaxis administered to their mothers before the delivery. The fecal flora was cultured on nonselective and selective media in infants 3 to 5, 10, 30, 60, and 180 days of age. Gastrointestinal signs were recorded daily by the mothers for 2 months. Results: The fecal colonization of infants born by cesarean delivery was delayed. Bifidobacterium-like bacteria and Lactobacillus-like bacteria colonization rates reached the rates of vaginally delivered infants at 1 month and 10 days, respectively. Infants born by cesarean delivery were significantly less often colonized with bacteria of the Bacteroides fragilis group than were vaginally delivered infants: At 6 months the rates were 36% and 76%, respectively (p = 0.009). The occurrence of gastrointestinal signs did not differ between the study groups. Conclusions: This study shows for the first time that the primary gut flora in infants born by cesarean delivery may be disturbed for up to 6 months after the birth. The clinical relevance of these changes in unknown, and even longer follow-up is needed to establish how long-lasting these alterations of the primary gut flora can be.
Our study showed that enteral administration of prophylactic probiotics in neonatal intensive care setup could significantly reduce morbidity due to necrotising enterocolitis in very low birth weight newborn. It also 
 Our study showed that enteral administration of prophylactic probiotics in neonatal intensive care setup could significantly reduce morbidity due to necrotising enterocolitis in very low birth weight newborn. It also helps in establishing early full enteral feeding and reduces hospital stay.
This Policy Statement was revised. See https://doi.org/10.1542/peds.2022-057988. This policy statement on breastfeeding replaces the previous policy statement of the American Academy of Pediatrics, reflecting the considerable advances that have occurred 
 This Policy Statement was revised. See https://doi.org/10.1542/peds.2022-057988. This policy statement on breastfeeding replaces the previous policy statement of the American Academy of Pediatrics, reflecting the considerable advances that have occurred in recent years in the scientific knowledge of the benefits of breastfeeding, in the mechanisms underlying these benefits, and in the practice of breastfeeding. This document summarizes the benefits of breastfeeding to the infant, the mother, and the nation, and sets forth principles to guide the pediatrician and other health care providers in the initiation and maintenance of breastfeeding. The policy statement also delineates the various ways in which pediatricians can promote, protect, and support breastfeeding, not only in their individual practices but also in the hospital, medical school, community, and nation.
Necrotizing enterocolitis, one of the most common and devastating diseases in neonates, typically manifests with feeding intolerance, abdominal distention, and bloody stools. This article discusses the current knowledge and treatment 
 Necrotizing enterocolitis, one of the most common and devastating diseases in neonates, typically manifests with feeding intolerance, abdominal distention, and bloody stools. This article discusses the current knowledge and treatment of this difficult-to-treat condition.
A enterocolite necrosante (EN) Ă© uma condição inflamatĂłria intestinal grave, que acomete principalmente recĂ©m-nascidos prematuros e de muito baixo peso ao nascer. Esta revisĂŁo narrativa objetivou reunir evidĂȘncias atuais sobre 
 A enterocolite necrosante (EN) Ă© uma condição inflamatĂłria intestinal grave, que acomete principalmente recĂ©m-nascidos prematuros e de muito baixo peso ao nascer. Esta revisĂŁo narrativa objetivou reunir evidĂȘncias atuais sobre os principais fatores de risco, mĂ©todos preventivos e condutas clĂ­nicas relacionadas Ă  EN. A busca bibliogrĂĄfica foi realizada em bases de dados eletrĂŽnicas como PubMed, Scopus, Embase, Cochrane Library e BVS, considerando publicaçÔes entre 2000 e 2025. Os achados indicam que a etiologia da EN Ă© multifatorial, envolvendo hipĂłxia-isquemia, disbiose intestinal, prĂĄticas alimentares inadequadas e uso irracional de medicamentos. EstratĂ©gias como o uso de leite materno exclusivo, controle de oxigenação, redução de antibiĂłticos desnecessĂĄrios e utilização de ferramentas de estratificação de risco, como o escore GutCheck(NEC), demonstraram impacto positivo na prevenção da doença. A revisĂŁo tambĂ©m destaca a importĂąncia do cuidado individualizado e da atualização constante das prĂĄticas clĂ­nicas com base em evidĂȘncias cientĂ­ficas. Conclui-se que, embora avanços tenham sido alcançados, ainda hĂĄ lacunas na compreensĂŁo da doença, exigindo novos estudos com maior rigor metodolĂłgico.
Probiotics are widely recognized for their health benefits, particularly in disease prevention and treatment. Recent research suggests that their therapeutic effects may be linked to the bacterial membrane vesicles (bMVs) 
 Probiotics are widely recognized for their health benefits, particularly in disease prevention and treatment. Recent research suggests that their therapeutic effects may be linked to the bacterial membrane vesicles (bMVs) they release. These nanoscale vesicles, secreted during probiotic growth and metabolism, facilitate intercellular communication through efficient material transport and signaling. With their biocompatibility and targeting properties, probiotic bMVs hold promise for medical applications. This review examines their biogenesis, bioactive components, functions, and role in disease treatment, while also discussing future research directions to unlock their full therapeutic potential.
The composition of the infant gut microbiome is critical to immune development and noncommunicable disease (NCD) trajectory. However, a comprehensive evaluation of the infant gut microbiome in the United States 
 The composition of the infant gut microbiome is critical to immune development and noncommunicable disease (NCD) trajectory. However, a comprehensive evaluation of the infant gut microbiome in the United States is lacking. The My Baby Biome study, designed to address this knowledge gap, evaluated the gut microbiomes of 412 infants (representative of U.S. demographic diversity) using metagenomics and metabolomics. Regardless of birth mode and/or feeding method, widespread Bifidobacterium deficit was observed, with approximately 25% of U.S. infants lacking detectable Bifidobacterium. Bifidobacterium-dominant microbiomes exhibit distinct features when compared to microbiomes with other dominant microbial compositions including reduced antimicrobial resistance and virulence factor genes, altered carbohydrate utilization pathways, and altered metabolic signatures. In C-section birth infants, Bifidobacterium tended to be replaced in the human milk oligosaccharide utilization niche with potentially pathogenic species. Longitudinal health outcomes from these infants suggest that the disappearance of key Bifidobacterium may contribute to the development of atopy.
Background/Objectives: Early childhood is a critical window of development, which is influenced by early life exposures including breastfeeding. Observational and preclinical studies have linked human milk oligosaccharides (HMOs) with neurocognitive 
 Background/Objectives: Early childhood is a critical window of development, which is influenced by early life exposures including breastfeeding. Observational and preclinical studies have linked human milk oligosaccharides (HMOs) with neurocognitive development. However, less attention has focused on behavioral outcomes including temperament and eating behaviors. Herein, we investigated the associations between HMO consumption and child temperament and child eating behaviors through four years of age. Methods: Participants were drawn from the STRONG Kids 2 cohort. Human milk was collected at 6 weeks postpartum, and HMO relative abundances were determined by HPLC-MS. Using validated questionnaires, child temperament was assessed at 3, 18, and 48 months of age, and child eating behaviors were measured at 12, 18, 24, 36, and 48 months of age. After adjusting for covariates, multiple linear regressions were carried out to assess the relationship between HMOs and the outcome measures. Results: The HMO profile of mothers showed two distinct clusters explained by maternal secretor status. Significant associations between HMO and surgency were only found in the full cohort and secretors, while more associations between HMO and negative affectivity were observed in non-secretors. A significant number of associations was observed between HMOs and child eating behaviors in full cohort, secretors, and non-secretors. HMO diversity, total fucosylation, and total sialylation were positively associated with food responsiveness, while neutral HMOs presented negative associations. However, these associations with food responsiveness were not observed in non-secretors. Conclusions: HMO profiles were associated with behavioral outcomes in the children, with variations by child age and maternal secretor status, highlighting the potential role of HMOs within the broader context of maternal and postnatal influences.
Background Biological barriers are essential for maintaining integrity and function and preventing microbial invasion. Maternal barrier dysfunction may play a role in preterm birth (PTB). However, the link between maternal 
 Background Biological barriers are essential for maintaining integrity and function and preventing microbial invasion. Maternal barrier dysfunction may play a role in preterm birth (PTB). However, the link between maternal barrier function and PTB is still unknown. This study aims to identify genetic evidence supporting the role of maternal barrier genes in PTB risk. Methods We examined 201 barrier-related genes to assess their association with PTB susceptibility. We utilized the FinnGen study, published literature's whole-genome sequencing (WGS) summary statistics and Early Growth Genetics (EGG) meta-analysis to identify the maternal barrier gene associated with PTB. Results Findings from the analysis of the maternal genome highlighted several barrier genes ( NOTCH1, LAMA4, F11R, MAGI1, MAGI2, TJP1, PARD3, CLDN10, CLDN14, CLDN15, GRHL3, CGNL1, LAMB2, RHOA , and LRP5 ) associated with PTB. Notably, NOTCH1 was supported by at least two independent genomic datasets. Conclusion The established roles of NOTCH1 in vascular barrier function, angiogenesis, decidualization, intestinal epithelial barrier, and inflammation support its mechanistic involvement. Our research enhances our understanding of maternal barrier genes linked to PTB, providing valuable insights for future prevention and intervention strategies.
Breastfeeding is essential for reducing infant morbidity and mortality, yet exclusive breastfeeding rates remain low, often due to insufficient milk supply. The molecular causes of low milk production are not 
 Breastfeeding is essential for reducing infant morbidity and mortality, yet exclusive breastfeeding rates remain low, often due to insufficient milk supply. The molecular causes of low milk production are not well understood. Fresh milk samples from 30 lactating individuals, classified by milk production levels across postpartum stages, were analyzed using genomic and microbiome techniques. Bulk RNA sequencing of milk fat globules (MFG), milk cells, and breast tissue revealed that MFG-derived RNA closely mirrors luminal milk cells. Transcriptomic and single-cell RNA analyses identified changes in gene expression and cellular composition, highlighting key genes (GLP1R, PLIN4, KLF10) and cell-type differences between low and high producers. Infant microbiome diversity was influenced by feeding type but not maternal milk supply. This study provides a comprehensive human milk transcriptomic catalog and highlights that MFG could serve as a useful biomarker for milk transcriptome analysis, offering insights into the genetic factors influencing milk production.
Background: Early identification and timely preventive interventions play an essential role for improving the prognosis of newborns with necrotizing enterocolitis (NEC). Thus, establishing a novel and simple prediction model is 
 Background: Early identification and timely preventive interventions play an essential role for improving the prognosis of newborns with necrotizing enterocolitis (NEC). Thus, establishing a novel and simple prediction model is of great clinical significance. Methods: The clinical data of 143 NEC neonates in the Zhujiang Hospital of Southern Medical University from October 2010 to October 2022 were collected, whereas 429 non-NEC patients in the same period were allocated to the control group by random sampling. Afterward, all participants were randomly divided into a training group (70%) and a testing group (30%). Then, five machine learning (ML) algorithms and classical logistic regression models were established, combining relevant clinical features and laboratory results. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of various models were compared to evaluate the performance of each model. Ten-folds cross-validation was used to find the best hyperparameters for each model. Decision curve analysis (DCA) was further used to evaluate the performance of the established models for clinical applications and create a column-line graph, ranking the feature importance in models by SHapely Additive exPlanation (SHAP). The column plots were calibrated using calibration curves. Additionally, the established model was validated in time series analysis and another medical center. Results: Six important features were included for modeling: days of age (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 1.08-1.25; p = 0.001), gestational age (OR = 0.77; 95% CI: 0.62-0.96; p = 0.018), eosinophil count (EOS) (OR = 3.78; 95% CI: 1.74-8.19; p < 0.001), hemoglobin (HB) (OR = 0.98; 95% CI: 0.97-1.00; p = 0.008), platelet distribution width (PDW) (OR = 1.18; 95% CI: 1.05-1.33; p = 0.004), and high-sensitivity C-reactive protein (HSCRP) (OR = 1.03; 95% CI: 1.01-1.06; p = 0.013). While the logistic regression model achieved an AUC of 0.904, accuracy of 0.865, sensitivity of 0.786, F1-score of 0.742, and a Brier score of 0.1009 in the training group, the AUCs for the five ML models ranged from 0.806 to 0.960. Among these models, the LightGBM model performed the best, providing an AUC of 0.960, accuracy of 0.858, sensitivity of 0.970, F1-score of 0.775, and a Brier score of 0.071. Conclusion: The LightGBM ML model can effectively identify neonatal patients at higher risk of NEC based on the day of age, gestational age, EOS, and HB, PDW, and HSCRP levels. Thus, this model is useful for assisting clinical decision-making.
Abstract Prematurity, defined as birth before 37 completed weeks of gestation, is the leading cause of mortality in children under five and affects approximately 11% of live births globally—around 15 
 Abstract Prematurity, defined as birth before 37 completed weeks of gestation, is the leading cause of mortality in children under five and affects approximately 11% of live births globally—around 15 million infants each year. Despite advances in neonatal care, preterm infants remain at an increased risk for a range of complications. One widely used clinical practice in neonatal intensive care units (NICUs) is the monitoring of gastric residuals (GRs) to assess feeding tolerance and guide enteral nutrition. While the clinical significance of GRs is debated, their microbial composition has not been extensively studied. In this study, we performed metagenomic sequencing of 199 stool and 69 GR samples from 39 preterm infants during hospitalization to characterize their gut and stomach microbiomes. To our knowledge, this is the first study to describe the microbial landscape of GR in preterm infants. We identified 11 distinct GR clusters, often dominated by Staphylococcus , Streptococcus , and Klebsiella , with microbial diversity correlating with GR aspiration frequency. Longitudinal analysis revealed temporal colonization patterns, with early dominance of Staphylococcus epidermidis and Bradyrhizobium , and later emergence of Escherichia coli , Staphylococcus hominis , and Streptococcus thermophilus . In stool samples, 8 microbial clusters were found, frequently enriched with Enterobacteriaceae . Early samples rich in S. epidermidis were associated with higher gestational age and lower microbial richness, while Bifidobacterium breve , a beneficial gut commensal, appeared later in hospitalization. Comparative analysis showed overlap between gut and gastric microbiota, though stomach samples were more dynamic and exhibited less intra-subject similarity. Strain-level resolution revealed both subject-specific (e.g., E. coli , K. pneumoniae ) and widely shared (e.g., S. epidermidis ) taxa. We also identified a pathogenic Klebsiella aerogenes strain associated with bacteremia with distinct genomic features a week ahead of its first clinical isolation. These findings provide novel insights into the dynamic and niche-specific microbial colonization of preterm infants.
Lacto-N-neotetraose (LNnT) is a key human milk oligosaccharide (HMO) with important prebiotic functions, supporting the growth of beneficial gut microbiota and contributing to infant health. Constructing plasmid-free strains via metabolic 
 Lacto-N-neotetraose (LNnT) is a key human milk oligosaccharide (HMO) with important prebiotic functions, supporting the growth of beneficial gut microbiota and contributing to infant health. Constructing plasmid-free strains via metabolic engineering for LNnT biosynthesis represents a feasible strategy for efficient industrial-scale production. This study integrates various strategies to construct plasmid-free strains capable of efficiently producing LNnT. Building on the previously developed Escherichia coli MG1655 strain for lacto-N-triose II (LNTri II) production, Hplex2B (encoding ÎČ1,4-galactosyltransferase) was incorporated, and its copy number was optimized to construct a complete and efficient biosynthetic pathway. By integrating an extra copy of the multidrug efflux pump gene mdfA, the strain tolerance was improved, resulting in a higher yield of LNnT. The integration of expression cassettes for key genes in the glycosyl donor synthesis pathway (including glmS, glmM, glmU, galU, and galE) with varying promoter strengths optimized the supply and balance. The subsequent removal of a key feedback inhibition circuit directed the reaction toward the synthesis of LNnT. The final strain, after successive optimization, produced LNnT at 7.76 g/L in shake flask culture and 34.24 g/L in a 5 L bioreactor, with precursor LNTri II concentrations of 0.58 g/L and 1.61 g/L, respectively.
Giriß: Nekrotizan enterokolit, prematĂŒre yenidoğanlarda görĂŒlen gastrointestinal bir hastalıktır. Bazı laboratuvar bulguları, erken tanı ve izlemde önemli rol oynayabilir. Bu çalıßmada, hemogram ve biyokimya laboratuvar parametrelerinin nekrotizan enterokolit tanı ve 
 Giriß: Nekrotizan enterokolit, prematĂŒre yenidoğanlarda görĂŒlen gastrointestinal bir hastalıktır. Bazı laboratuvar bulguları, erken tanı ve izlemde önemli rol oynayabilir. Bu çalıßmada, hemogram ve biyokimya laboratuvar parametrelerinin nekrotizan enterokolit tanı ve takibindeki önemini değerlendirmeyi amaçladık. Yöntemler: Çalıßmamıza nekrotizan enterokolit tanısı almıß 115 hasta ve nekrotizan enterokolit gelißmeyen ve diğer nedenlerle takip edilen 115 hastadan olußan kontrol grubu dahil edildi. Laboratuvar bulguları karßılaßtırılmıßtır. Sonuçlar: Nekrotizan enterokolit grubunda kontrol grubuna göre doğumda bakılan glukoz, alanin aminotransferaz, aspartat aminotransferaz, sodyum, potasyum, hemoglobin, hematokrit, trombosit ve ortalama trombosit hacmi dĂŒzeyleri anlamlı ßekilde daha dĂŒĆŸĂŒk, beyaz kan hĂŒcresi dĂŒzeyi ise daha yĂŒksek saptanmıßtır (p
Background The limited availability and high cost of human milk fortifier (HMF) in developing countries represent significant challenges. Preterm formula (PTF) fortification of breast milk is a potential alternative, but 
 Background The limited availability and high cost of human milk fortifier (HMF) in developing countries represent significant challenges. Preterm formula (PTF) fortification of breast milk is a potential alternative, but its safety and impact on growth are still uncertain. This study compares the safety and effect of breast milk fortification with PTF versus HMF on growth velocity in very low birth weight preterm infants. Methods A thorough literature search was conducted in the PubMed, Scopus, Google Scholar, ClinicalTrials.gov , and Europe PMC databases up to March 24, 2024. Relevant randomized controlled trials (RCTs) studying fortifying breast milk with PTF or HMF were identified and their quality assessed using the Cochrane Risk of Bias 2 tool. Statistical analysis was performed in Review Manager Web, and certainty of evidence was assessed with GRADE. Results Six RCTs were included, of which one exhibited low bias risk, three had moderate concerns, and two were classed as high risk. The six RCTs, involving 434 preterm infants, revealed no significant differences in the gain of weight (SMD 0, 95% CI −0.19 to 0.19), length (MD −0.01 cm/wk, 95% CI −0.06 to 0.05), or head circumference (MD −0.01 cm/wk, 95% CI −0.06 to 0.04) between PTF and HMF. There were comparable risks of morbidities. Conclusion Very low certainty evidence suggests that breast milk fortification with PTF may be a safe alternative to HMF, with similar safety profiles and effects on growth.
Background and Objectives: Infant feeding practices play a crucial role in shaping the oral microbiome, modulating inflammatory responses, and maintaining epithelial health during the first year of life. Breastfeeding promotes 
 Background and Objectives: Infant feeding practices play a crucial role in shaping the oral microbiome, modulating inflammatory responses, and maintaining epithelial health during the first year of life. Breastfeeding promotes the growth of beneficial bacteria and supports a diverse, stable microbial community. In contrast, formula feeding is associated with increased colonization by potentially pathogenic bacteria, such as Staphylococcus and Escherichia coli, which may elevate the risk of infections, oral diseases, and inflammation. This study investigates the effects of breastfeeding versus formula feeding on oral bacterial growth, epithelial cell integrity, and interleukin-17 (IL-17) expression in infants aged 1-12 months. Materials and Methods: A total of 60 infants (30 breastfed and 30 formula-fed) were recruited from pediatric clinics in the Qassim region. Microbial cultures quantified bacterial colony-forming units (CFUs), and epithelial cell morphology was assessed through the microscopic analysis of mucosal scrapings. IL-17 concentrations were quantified from the oral mucosa through enzyme-linked immunosorbent assay. Statistical analyses, including t-tests and chi-square tests, compared bacterial loads, IL-17 levels, and indicators of epithelial health between groups. Adjustment for potential confounders was achieved through multivariate statistical analysis. Results: Formula-fed infants showed significantly higher IL-17 levels than breastfed infants (p < 0.001), indicating a stronger pro-inflammatory profile. Breastfed infants exhibited lower inflammation, improved epithelial health, and reduced cellular debris compared to formula-fed infants, who had higher bacterial loads. A significant correlation was found between epithelial health and bacterial clustering, with clearer epithelial cells associated with lower bacterial colonization. Conclusions: Formula feeding was associated with increased salivary IL-17 levels, greater bacterial colonization, and compromised epithelial integrity, indicating a heightened pro-inflammatory state and potential vulnerability to mucosal irritation or infection. Breastfeeding appeared to confer protective effects by promoting healthier microbial balance, epithelial integrity, and reducing inflammatory responses. These findings underscore the immunological and microbial benefits of breastfeeding in supporting oral health during infancy.
ABSTRACT Background Experts recommend assessing preterm infant growth against fetal growth patterns. However, obtaining accurate estimates of healthy fetal growth from preterm infants is challenging as many had intrauterine faltering 
 ABSTRACT Background Experts recommend assessing preterm infant growth against fetal growth patterns. However, obtaining accurate estimates of healthy fetal growth from preterm infants is challenging as many had intrauterine faltering growth. Objectives To improve preterm infant growth assessments by developing Fenton third‐generation sex‐specific preterm growth charts based on anthropometric distributions of preterm infants without abnormal fetal growth. We also aimed to evaluate the consistency of the new charts' growth velocities. Data Sources From the last search for the 2013 Fenton growth charts to November 2024, MEDLINE and EMBASE databases, grey literature, as well as US Vital statistics and iNeo Consortium. Study Selection and Data Extraction We followed systematic review methodology to identify population‐based sex‐specific anthropometric estimates of preterm cohorts without abnormal fetal growth beginning ≀ 24 weeks of gestation. Specified a priori, outcomes included newborn sex‐specific estimates of birthweight, length, and head circumference. Synthesis We followed PRISMA guidelines. Literature screening and quality assessment were performed in duplicate. We harmonised weight, length, and head circumference weighted‐average meta‐analyses with the World Health Organization growth standard and rescaled the charts' x ‐axis from completed gestational weeks to exact gestational age (weeks and days). Results Seven studies from 15 countries (Australia, Brazil, Canada, China, Finland, Israel, Italy, Japan, Netherlands, New Zealand, Sweden, Switzerland, Spain, United Kingdom and United States) were included, representing 4.8 million births 22–42 weeks of gestation. 174,184 were &lt; 30 weeks gestational age. The Fenton third‐generation preterm growth charts' weights showed improved growth velocity across percentiles with consistent declines for weight, length and head circumference velocity as post‐menstrual age increased. The birthweight meta‐analysis curves had similar shapes to fetal ultrasound estimates. Conclusions The Fenton third‐generation preterm infant growth chart curves demonstrate improved and more uniform slopes across percentiles and closer alignment with fetal ultrasound estimates, offering a growth standard for preterm infants. Prospero Registration CRD42024589756
Introducción: La leche materna es la principal fuente de nutrición en los primeros meses de vida del lactante, destacando por su contenido energético, bioactivo y de åcidos grasos esenciales como 
 Introducción: La leche materna es la principal fuente de nutrición en los primeros meses de vida del lactante, destacando por su contenido energético, bioactivo y de åcidos grasos esenciales como DHA y EPA. Su composición, aunque relativamente estable, puede verse modificada por el patrón alimentario materno, influyendo en la digestión y tolerancia del neonato. Ademås, tras su extracción, la acidez de la leche puede aumentar debido a la proliferación bacteriana, lo que deteriora su calidad nutricional e inmunológica, siendo un riesgo para la salud del bebé. Metodología: Se realizó un estudio cuantitativo, descriptivo y transversal con una muestra de 24 madres lactantes con hijos menores de seis meses. La información fue recolectada mediante un cuestionario estructurado, validado y autoadministrado de forma digital, enfocado en identificar håbitos alimentarios maternos y conocimientos sobre alimentación complementaria infantil. Resultados: Las madres demostraron buen conocimiento sobre la importancia de una dieta equilibrada durante la lactancia, lo que favorece la calidad de la leche materna. Sin embargo, se identificaron deficiencias en temas clave como la alimentación complementaria y el adecuado manejo post-extracción de la leche, lo que podría afectar la salud del lactante. Discusión: Aunque existe una base sólida de conocimiento materno, persisten vacíos sobre pråcticas específicas como el inicio, frecuencia y tipo de alimentos complementarios, así como el impacto del almacenamiento de la leche en su acidez y seguridad. Conclusión: Reforzar la educación nutricional integral desde el embarazo es fundamental para garantizar una leche materna de calidad y una nutrición infantil adecuada.
Necrotizing enterocolitis (NEC) is a leading cause of death among preterm neonates, leading to increased hospital care and economic burden. Based on all the available randomized control trials and observational 
 Necrotizing enterocolitis (NEC) is a leading cause of death among preterm neonates, leading to increased hospital care and economic burden. Based on all the available randomized control trials and observational studies to date, the peritoneal drain placement is most likely associated with higher mortality than laparotomy when the NEC diagnosis is made prior to the intervention. Peritoneal drainage, however, may be utilized as a bridge treatment in cases where early operation is not possible due to clinical instability or not immediately available. Unfortunately, most studies lack histopathological confirmation of radiographic abnormalities corresponding to NEC or spontaneous intestinal perforation (SIP). Such large prospective studies evaluating the impact of peritoneal drain and laparotomy, which utilize pre-determined histopathologic definitions of NEC/SIP, are necessary to optimize clinical outcomes.
Background Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal emergency in preterm neonates, with mortality exceeding 50% in severe cases. Early diagnosis remains challenging due to nonspecific clinical signs. Objectives This 
 Background Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal emergency in preterm neonates, with mortality exceeding 50% in severe cases. Early diagnosis remains challenging due to nonspecific clinical signs. Objectives This study aimed to evaluate the diagnostic accuracy of fecal calprotectin (FCP) and assess Doppler ultrasound (US) for predicting disease severity and mortality. Methods A case-control study of 54 neonates with NEC (Bell’s Stages I–III) and 42 matched controls. FCP levels were measured within 48 hours of symptom onset and Doppler US was performed to evaluate bowel perfusion. It was done at Neonatal Intensive Care Unit (NICU) during the period from (January 2019 to December 2019). Results Fecal calprotectin levels were significantly higher in NEC cases (362.6 ± 239.8 ”g/g) compared to controls (61.9 ± 44.2 ”g/g, p &lt; 0.001). The optimal FCP cutoff was 176 ”g/g (sensitivity 87%, specificity 97.6%). Doppler US showed decreased bowel perfusion in 77.8% of Stage III NEC cases, which strongly predicted mortality (OR 4.2, 95% CI 1.8–9.6). Conclusion FCP and Doppler US provide complementary, non-invasive methods for early NEC diagnosis and risk stratification. Their combined use could improve clinical decision-making in high-risk neonates.
Necrotizing enterocolitis (NEC) is a potentially fatal comorbidity of prematurity with one in five affected requiring surgical intervention. Despite its seriousness, there is lack of objective radiographic criteria on plain 
 Necrotizing enterocolitis (NEC) is a potentially fatal comorbidity of prematurity with one in five affected requiring surgical intervention. Despite its seriousness, there is lack of objective radiographic criteria on plain abdomnial radiographs (X-ray) to guide prognosis and decision making. Point of care bowel ultrasound (BUS) provides a more dynamic assessment and more information around bowel health. However, there is lack of widespread adoption of this practice by neonatologists due to training opportunities and inconsistent support from radiologists. We present a feasibility study from UK of using point of care bowel ultrasound in conjunction with X-ray to aid diagnosis of NEC. We report that that neonatologist performed BUS when used as an additional diagnostic aid has a higher positive predictive value and specificity compared to X-rays alone. Features like absent or poor peristalsis and abnormal bowel perfusion were the most consistent pathological findings in our cohort. Wider implementation of this practice is limited by training opportunities and dedicated support from radiology team
Lactoferrin is known to exhibit broad spectrum activity against a multitude of bacteria, fungi, and viruses due to its multi-functional mode of action. Recently, Lactea Therapeutics and its affiliates have 
 Lactoferrin is known to exhibit broad spectrum activity against a multitude of bacteria, fungi, and viruses due to its multi-functional mode of action. Recently, Lactea Therapeutics and its affiliates have developed a novel, patent-pending technology to purify naturally derived bovine lactoferrin (Lactea Lf) for use as a medical countermeasure that was not previously available. To assess the efficacy of Lactea Lf against biothreat pathogens, we performed biofilm inhibition assays and generated dose-response curves against Burkholderia pseudomallei , Burkholderia mallei , and Francisella tularensis for proof-of-principle studies. Here, we show that Lactea Lf can significantly inhibit biofilm and decrease the overall growth in a dose dependent manner for all Burkholderia species tested. Of note, Lactea Lf was found to completely inhibit biofilm formation by virulent B. pseudomallei without observing complete growth inhibition. The growth of F. tularensis was also significantly inhibited when cultured in the presence of Lactea Lf and appeared more sensitive to treatment when compared to B. pseudomallei . Based on these results, a pneumonic infection model using the F. tularensis LVS strain was performed prophylactically administering Lactea Lf and continuing treatment post challenge. No protection was observed in this model which prompted biodistribution studies using fluorescent tagged Lactea Lf. These experiments revealed that therapeutic material was mainly confined to the NALT region following intranasal delivery and then quickly dispersed or inactivated suggesting that future formulation and delivery method could be addressed to increase in vivo treatment efficacy. Taken together, these data support that Lactea Lf is a potentially new candidate for further studies as a broad-spectrum antimicrobial medical countermeasure with efficacy against several high priority biodefense-related bacterial pathogens.
<title>Abstract</title> Background Early modulation of the neonatal gut microbiota is emerging as a strategy to mitigate late-onset sepsis (LOS) and enhance enteral feeding tolerance in high-risk infants. Postbiotics—non-viable microbial preparations 
 <title>Abstract</title> Background Early modulation of the neonatal gut microbiota is emerging as a strategy to mitigate late-onset sepsis (LOS) and enhance enteral feeding tolerance in high-risk infants. Postbiotics—non-viable microbial preparations with immunomodulatory metabolites—may offer probiotic-like benefits while avoiding the risks associated with live organisms. We compared a daily postbiotic–synbiotic blend with bovine lactoferrin, another milk-derived bioactive, in preterm and surgical neonates. Methods In a single-centre, randomised (1:1), open-label trial conducted in a tertiary NICU (January 2022–March 2024), 130 infants (mean gestational age 34 ± 3 weeks; 44 with major surgical conditions) received either (i) 1 mL·day⁻Âč of a preparation containing 2â€Č-fucosyllactose, lactase, and heat-inactivated <italic>Lactobacillus acidophilus</italic> (10âč cells) or (ii) bovine lactoferrin 100 mg·day⁻Âč. Primary endpoint was culture-proven sepsis; secondary endpoints included time to full enteral feeds, days of parenteral nutrition, length of stay (LOS), discharge weight, and colonisation rates. Categorical data were analysed with χÂČ/Fisher’s exact test; continuous variables with Mann–Whitney U or <italic>t</italic>-test as appropriate (α = 0.05). Results Overall sepsis incidence was low (7.7%) and did not differ significantly between groups (postbiotic 3/65 vs lactoferrin 7/65, <italic>P</italic> = 0.39). The postbiotic cohort achieved complete enteral feeding markedly earlier (median 8.3 ± 4.7 days vs 30 ± 8.3 days; <italic>P</italic> &lt; 0.001), required fewer parenteral-nutrition days, and had a shorter LOS (20.6 ± 17 vs 29 ± 20 days; <italic>P</italic> = 0.01). Discharge weight was higher in the postbiotic group (2872 ± 632 g vs 2695 ± 335 g; <italic>P</italic> = 0.04). Colonisation rates were comparable. Conclusions A synbiotic postbiotic formulation accelerated transition to full enteral nutrition, reduced hospital stay, and improved growth without increasing colonisation or sepsis risk relative to lactoferrin. Larger, multi-centre trials are warranted to confirm potential infection-protective effects and to explore synergistic combinations of postbiotics with lactoferrin in vulnerable neonatal populations.
The intestinal epithelial barrier consists of a single layer of cells that separate the gut lumen from the rest of the body. It regulates and protects the intestinal tract immunologically 
 The intestinal epithelial barrier consists of a single layer of cells that separate the gut lumen from the rest of the body. It regulates and protects the intestinal tract immunologically and mechanically. Necrotizing enterocolitis (NEC) is one of the most common conditions requiring emergency surgery in the neonatal intensive care unit and is associated with a septic shock-like state contributing to multi-organ dysfunction. NEC affects 6–10% of very low birthweight infants and remains a leading cause of death. This review presents current evidence of the role of tight junction proteins in clinical neonatology and intestinal health using information from our own clinical and laboratory research in conjunction with information collected from an extensive search in the databases PubMed, EMBASE, and Scopus. The ability to measure the permeability of the intestinal barrier in real-time is essential to understanding the disease process of NEC and the subsequent morbidities. Detection of TJ proteins in blood and stool of preterm infants represents a potential biomarker for the early NEC diagnosis. Therapeutics targeting TJ proteins may also mitigate NEC severity and improve clinical outcomes.
Background Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections, particularly in infants and the older population, with limited effective treatments available. Cordycepin, lactoferrin, and Sargassum fusiforme 
 Background Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections, particularly in infants and the older population, with limited effective treatments available. Cordycepin, lactoferrin, and Sargassum fusiforme polysaccharides (CLS) are natural compounds with antiviral and immunomodulatory properties. This study investigates the therapeutic potential of CLS in RSV infection. Methods A murine model of RSV infection was used to evaluate the effects of CLS. Lung pathology was assessed by lung index, histology, and bronchoalveolar lavage fluid (BALF) albumin and LDH levels. Viral load was measured by RSV mRNA and protein expression. Alveolar macrophage depletion was achieved using clodronate liposomes, and macrophage polarization was analyzed via flow cytometry and RT-qPCR. Results CLS treatment improved lung pathology, reduced BALF injury markers, and decreased viral load. The therapeutic effects of CLS were abrogated by macrophage depletion, indicating a reliance on alveolar macrophages. CLS promoted M2-like macrophage polarization, increasing M2 markers and reducing M1 markers. In vitro , CLS reduced RSV-induced apoptosis and enhanced macrophage proliferation. Conclusions CLS protects against RSV-induced lung injury by promoting M2-like macrophage polarization and reducing viral load. These findings support CLS as a potential therapeutic for RSV infections.
BACKGROUND Necrotizing enterocolitis (NEC) remains a prominent gastrointestinal emergency among infants, particularly term infants with congenital heart defects (CHD) being at high risk. The molecular processes that contribute to NEC 
 BACKGROUND Necrotizing enterocolitis (NEC) remains a prominent gastrointestinal emergency among infants, particularly term infants with congenital heart defects (CHD) being at high risk. The molecular processes that contribute to NEC have yet to be completely understood. The high mortality rates necessitate an active search for noninvasive biomarkers that can aid in the preclinical diagnosis and prognosis of NEC. MicroRNAs (miRs), which are involved in many biological processes in both health and disease, have been discovered to play an important role in regulating inflammation and immune responses via various signaling pathways. AIM To determine the plasma levels of miR-155, miR-221, miR-223, miR-320a, miR-451a as potential NEC biomarkers in term newborns with CHD. METHODS This prospective cohort study included twenty-tree term newborns with CHD who underwent cardiac surgery on the median day of life (DOL) = 7. Nine of them developed NEC (Bell’s stage IIA and IIIA) within 1 week of cardiac surgery (NEC newborns). Blood samples were collected before (median DOL = 5) and following (median DOL = 13) cardiac surgery. Levels of plasma miR-155-5p, miR-221-3p, miR-223-3p, miR-320a-3p, and miR-451a were determined using real-time polymerase chain reaction. The functional analysis was executed using the DIANA-miRPath v4.0. RESULTS Preoperatively, NEC newborns had significantly lower plasma levels of miR-155 (2.70-fold, P = 0.020), miR-223 (2.42-fold, P = 0.030), and miR-320a (3.62-fold, P = 0.006) than newborns without NEC. Postoperatively, miR-451a levels differed significantly between the newborn groups, showing a 4.70-fold decrease (P = 0.014) in expression when clinical NEC symptoms appeared. According to receiver operating characteristic analysis, miR-320a was found to be the most effective predictive biomarker for NEC [area under the curve (AUC) = 0.835, 63% sensitivity, 100% specificity], while miR-451a was identified as a NEC biomarker (AUC = 0.835, 85.7% sensitivity, 76.9% specificity). Preoperatively, miR-155-5p, miR-223-3p, and miR-320a-3p were differentially expressed and targeted the forkhead box O and Hippo pathways (P &lt; 0.01). CONCLUSION Our study demonstrates, for the first time, that plasma miR-320a-3p levels can be used as a preclinical biomarker for NEC in term newborns with CHD.
Kamaldeep | IP Journal of Paediatrics and Nursing Science
Lacto-N-fucopentaose I (LNFP I), a fucosylated neutral human milk oligosaccharide (HMO) with diverse biological functions, was biosynthesized through metabolic engineering in Escherichia coli BL21star (DE3). A de novo pathway was 
 Lacto-N-fucopentaose I (LNFP I), a fucosylated neutral human milk oligosaccharide (HMO) with diverse biological functions, was biosynthesized through metabolic engineering in Escherichia coli BL21star (DE3). A de novo pathway was constructed by chromosomal integration of three key enzymes: lgtA (ÎČ-1,3-N-acetylglucosaminyltransferase), wbdO (ÎČ-1,3-galactosyltransferase), and galE (UDP-galactose-4-epimerase), generating a plasmid-free strain that achieved a lacto-N-tetraose (LNT) titer of 109.80 g/L in a 5 L bioreactor, the highest yield reported to date. Subsequent screening identified α-1,2-fucosyltransferase (FutC) from Helicobacter pylori as the optimal catalyst for LNFP I biosynthesis. Multidimensional optimization strategies were systematically implemented, including copy number balancing of rate-limiting transferases, promoter-RBS engineering, enhanced intracellular cofactor regeneration, and knockout of competing pathways. Fed-batch fermentation under optimized conditions yielded 77 g/L LNFP I with 93.05% LNT-to-LNFP I conversion efficiency, representing both the highest reported titer and precursor utilization efficiency for LNFP I.
ABSTRACT Introduction Necrotising enterocolitis (NEC) is a life‐threatening intestinal disease of the newborn characterised by ischaemia, inflammation and bowel necrosis. Due to the lack of biochemical markers and nonspecific clinical 
 ABSTRACT Introduction Necrotising enterocolitis (NEC) is a life‐threatening intestinal disease of the newborn characterised by ischaemia, inflammation and bowel necrosis. Due to the lack of biochemical markers and nonspecific clinical signs in early NEC, bowel ultrasound has gained popularity as a diagnostic tool. This survey aimed to investigate the opinions of neonatal clinicians on the practice of point‐of‐care bowel ultrasound for the diagnosis of NEC. Methods This quantitative study utilised a cross‐sectional online single‐invitation survey sent to neonatal clinicians using point‐of‐care ultrasound across Australia, New Zealand and Singapore. We aimed to explore the barriers to, and facilitators of the clinical practice of bowel ultrasound in NEC using the survey responses. Results The survey results indicate a clear need for a dedicated training module in Australasia to equip neonatal clinicians with the skills for point‐of‐care bowel ultrasound assessment. Most (95%) of neonatal clinicians practising point‐of‐care ultrasound agreed that performing a bowel ultrasound in the suspected diagnosis of NEC is helpful or may be helpful, with 87% expressing interest in undertaking training. Conclusion The study's findings reveal a strong interest among neonatal clinicians in Australia and New Zealand to learn point‐of‐care bowel ultrasound for NEC diagnosis. This interest not only sets the stage for a collaborative approach in planning and developing a training programme but also has the potential to significantly improve NEC diagnosis and patient outcomes in clinical practice.
As the limit of viability is extended to lower gestational ages, neonatologists caring for preterm infants must discover the optimal nutritional combination to support postnatal growth. It has been well 
 As the limit of viability is extended to lower gestational ages, neonatologists caring for preterm infants must discover the optimal nutritional combination to support postnatal growth. It has been well established that introducing protein soon after birth is associated with improved short-term growth at 36 weeks postmenstrual age and neurodevelopment. However, it remains unclear what the optimal level of protein is for parenteral nutrition at various gestational ages. Several studies have shown possible adverse effects of high-protein delivery in very low birth weight infants. Inborn errors in amino acid metabolism also caution us that higher levels of specific amino acids can harm the growing brain.
Abstract Human milk has a low microbial biomass with a microbiome dominated by typical skin and oral taxa, raising concerns about contamination during sample collection. However, to date, no study 
 Abstract Human milk has a low microbial biomass with a microbiome dominated by typical skin and oral taxa, raising concerns about contamination during sample collection. However, to date, no study has directly compared samples collected with and without aseptic technique, leaving questions related to potential contamination within the field. To address this, we compared the microbiota of hand-expressed milk samples collected from 23 mothers before and after cleansing of the hands and breast. Metataxonomic analysis showed that taxonomic profiles were largely unaffected by cleansing, with only Rothia mucilaginosa significantly more abundant in non-aseptically collected samples (P = 0.007). Although aseptically and non-aseptically collected samples were taxonomically similar, there was a higher level of bacterial richness (P = 0.003) and evenness (Shannon diversity, P = 0.0002) in non-aseptically collected samples, suggesting that multiple low-abundance taxa are introduced via skin contamination. These findings support the use of aseptic collection methods to minimise external contamination and accurately assess milk microbial diversity. Importantly, they also suggest that common skin and oral taxa detected in human milk are likely true members of the mammary microbiome.
Background: Lung cancer is the leading cause of cancer-related deaths worldwide, and to date, standard chemotherapeutic drugs kill normal cells non-selectively. Recently, lactoferrin has been reported to show anticancer properties 
 Background: Lung cancer is the leading cause of cancer-related deaths worldwide, and to date, standard chemotherapeutic drugs kill normal cells non-selectively. Recently, lactoferrin has been reported to show anticancer properties with high selectivity through pyroptosis. Therefore, this study aimed to provide insights into how bovine lactoferrin induces cytotoxicity by altering the cell cycle, reactive oxygen species (ROS) production, and mitochondrial membrane potential and by in-ducing pyroptosis in A549 cells. Methods: Our study employed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to measure cell viability after lactoferrin treatment. Cell cycle analysis was conducted using propidium iodide (PI), followed by flow cytometry. To determine the ROS fold change, treated cells were stained with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (DCFH-DA), which emits fluorescence upon oxidation. Mitochondrial membrane potential (MMP) was measured with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) dye to determine the ratio of red to green fluorescence. Pyroptotic protein expressions were identified through western blot analysis. Results: Lactoferrin-induced cytotoxity on A549 cells increased in a concentration-dependent man-ner. Cell cycle analysis revealed an increase in the population at both the subG1 and G0/G1 phases, accompanied by a decrease in the S and G2/M phases, indicating DNA fragmentation and a G0/G1 phase arrest. ROS fold change and MMP initially increased but subsequently declined with lactoferrin concentrations. Finally, all targeted pyroptotic proteins were regulated in treated cells. Conclusion: Our study shows that lactoferrin has potential as an alternative treatment for lung ade-nocarcinoma by trigerring pyroptosis in A549 cells, primarily through the caspase-1, caspase-4 and GSDMD pathways.