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The nutritional adequacy of human milk (HM) from vegan/vegetarian mothers has been a matter of debate, and a variety of recommendations regarding the eligibility of these mothers as human milk donors exists. According to the latest evidence, HM from vegans/vegetarians is similar in its composition to that from omnivores, however, some differences may be observed regarding vitamin B12 and omega-3 fatty acids concentrations. Maternal supplementation of these compounds has been proven effective in increasing their HM concentration. With this survey, we aimed to explore the practices currently in use in European human milk banks (HMBs) regarding potential donors following vegan/vegetarian diets. The online survey was distributed to European HMBs between January and July 2022. A total of 188 HMBs were contacted, and 118 replied (response rate 63%). Vegan and vegetarian mothers were recommended supplements of vitamin B12 to be accepted as donors in 27% and 26% of HMBs, respectively. Additional omega-3 fatty acid supplementation was required in 8% HMBs. In the remaining HMBs, these mothers were either systematically excluded or included regardless of supplementation. The dosage of the recommended supplements was extremely variable. Fifty-one percent of HMBs were following recommendations to guide their practice, national or local recommendations mainly. Great variability in European HMBs practices towards potential donors following vegan/vegetarian diets exists. Some of these practices can result in loss of donors and/or in potential nutritional deficiencies. Standardised evidence-based recommendations on this issue and their implementation in daily HMB practice are needed.
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Bancos de Leche Humana , Veganos , Humanos , Leche Humana , Dieta Vegetariana , Vegetarianos , Vitamina B 12 , Vitaminas , DietaRESUMEN
BACKGROUND: It is known that breastfeeding protects the infant from enteric and respiratory infections; however, the antiviral properties of human milk against enteric and respiratory viruses are largely unexplored. RESEARCH AIMS: To explore the antiviral activity of human preterm colostrum against rotavirus and respiratory syncytial virus and to assess whether the derived extracellular vesicle contribute to this activity. METHODS: We used a cross-sectional, prospective two-group non-experimental design. Colostra were collected from mothers of preterm newborns (N = 10) and extracellular vesicles were purified and characterized. The antiviral activity of colostra and derived extracellular vesicles were tested in vitro against rotavirus and respiratory syncytial virus and the step of viral replication inhibited by extracellular vesicles was investigated. RESULTS: Each sample of colostrum and colostrum-derived extracellular vesicles had significant antiviral activity with a wide interpersonal variability. Mechanism of action studies demonstrated that extracellular vesicles acted by interfering with the early steps of the viral replicative cycle. CONCLUSION: We demonstrated the intrinsic antiviral activity of human colostrum against rotavirus and respiratory syncytial virus and we showed that extracellular vesicles substantially contribute to the overall protective effect. Our results contribute to unravelling novel mechanisms underlying the functional role of human milk as a protective and therapeutic agent in preterm infants.
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Calostro/química , Vesículas Extracelulares , Virus Sincitiales Respiratorios , Rotavirus , Animales , Lactancia Materna , Línea Celular , Chlorocebus aethiops , Estudios Transversales , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Embarazo , Estudios Prospectivos , Replicación ViralRESUMEN
Fortification of human milk (HM) for preterm and very low-birth weight (VLBW) infants is a standard practice in most neonatal intensive care units. The optimal fortification strategy and the most suitable protein source for achieving better tolerance and growth rates for fortified infants are still being investigated. In a previous clinical trial, preterm and VLBW infants receiving supplementation of HM with experimental donkey milk-based fortifiers (D-HMF) showed decreased signs of feeding intolerance, including feeding interruptions, bilious gastric residuals and vomiting, with respect to infants receiving bovine milk-based fortifiers (B-HMF). In the present ancillary study, the urinary metabolome of infants fed B-HMF (n = 27) and D-HMF (n = 27) for 21 days was analyzed by 1H NMR spectroscopy at the beginning (T0) and at the end (T1) of the observation period. Results showed that most temporal changes in the metabolic responses were common in the two groups, providing indications of postnatal adaptation. The significantly higher excretion of galactose in D-HMF and of carnitine, choline, lysine and leucine in B-HMF at T1 were likely due to different formulations. In conclusion, isocaloric and isoproteic HM fortification may result in different metabolic patterns, as a consequence of the different quality of the nutrients provided by the fortifiers.
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Nutrición Enteral/métodos , Alimentos Fortificados , Recien Nacido Prematuro/orina , Leche Humana/metabolismo , Estado Nutricional , Animales , Carnitina/orina , Bovinos , Colina/orina , Equidae , Femenino , Galactosa/orina , Humanos , Recién Nacido , Leucina/orina , Lisina/orina , Masculino , Metaboloma , Leche Humana/químicaRESUMEN
Oxysterols are cholesterol oxidation derivatives. Those containing an additional hydroxyl group on the side chain of the cholesterol molecule result from a physiological enzymatic synthesis and include the majority of oxysterols present in the circulation. Among these, 25-hydroxycholesterol (25OHC) and 27-hydroxycholesterol (27OHC) are characterized by a broad antiviral activity and are now considered involved in the innate immune response against viruses. Despite the emerging role of these sterols in the innate antiviral defences, no data are available on their presence in human breast milk (BM) to date. In this study, we investigated the content of oxysterols of enzymatic synthesis in BM of twelve donor mothers at different stages of lactation (i.e. in colostrum, transitional milk, and mature milk) by gas chromatography-mass spectrometry analysis. The side-chain oxysterols 25OHC, 27OHC, and 24S-hydroxycholesterol (24SOHC) were actually present in BM in all stages of lactation, but the concentration of 27OHC showed a remarkable peak in colostrum. Antiviral assays revealed that all the colostrum samples contained 27OHC concentrations that were active in vitro against two relevant pediatric viral pathogens: the human rotavirus and the human rhinovirus. Overall, this study discloses new antiviral components of BM and suggests a passive transfer of these protective factors to the infant via breastfeeding, especially in the first few days of lactation.
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Antivirales/análisis , Leche Humana/química , Oxiesteroles/análisis , Adulto , Animales , Antivirales/sangre , Antivirales/farmacología , Línea Celular , Chlorocebus aethiops , Calostro/química , Femenino , Humanos , Lactancia , Oxiesteroles/sangre , Oxiesteroles/farmacología , Rhinovirus/efectos de los fármacos , Rotavirus/efectos de los fármacosRESUMEN
Evidence indicates that human milk (HM) is the best form of nutrition uniquely suited not only to term but also to preterm infants conferring health benefits in both the short and long-term. However, HM does not provide sufficient nutrition for the very low birth weight (VLBW) infant when fed at the usual feeding volumes leading to slow growth with the risk of neurocognitive impairment and other poor health outcomes such as retinopathy and bronchopulmonary dysplasia. HM should be supplemented (fortified) with the nutrients in short supply, particularly with protein, calcium, and phosphate to meet the high requirements of this group of babies. In this paper the European Milk Bank Association (EMBA) Working Group on HM Fortification discusses the existing evidence in this field, gives an overview of different fortification approaches and definitions, outlines the gaps in knowledge and gives recommendations for practice and suggestions for future research. EMBA recognizes that "Standard Fortification," which is currently the most utilized regimen in neonatal intensive care units, still falls short in supplying sufficient protein for some VLBW infants. EMBA encourages the use of "Individualized Fortification" to optimize nutrient intake. "Adjustable Fortification" and "Targeted Fortification" are 2 methods of individualized fortification. The quality and source of human milk fortifiers constitute another important topic. There is work looking at human milk derived fortifiers, but it is still too early to draw precise conclusions about their use. The pros and cons are discussed in this Commentary in addition to the evidence around use of fortifiers post discharge.
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OBJECTIVES: This study aimed to investigate the anti-human cytomegalovirus (CMV) activity of milk from seropositive and seronegative mothers of preterm infants and to analyze its changes throughout the different stages of lactation and after Holder pasteurization, a procedure adopted by donor human milk banks. METHODS: Eighteen mothers of preterm infants were enrolled in the study. Colostrum, transitional milk, and mature milk samples were collected and tested for anti-CMV activity. Depletion of immunoglobulins A from milk samples was carried out by jacalin resin. Pools of milk samples were pasteurized according to Holder technique. RESULTS: All samples were endowed with anti-CMV activity, although to a different extent. In CMV IgG-positive mothers, colostra were significantly more active than the transitional milk and mature milk samples. Moreover, they were more potent than colostra from seronegative mothers. Immunoglobulins A depletion in colostra from IgG-positive mothers resulted in a partial loss of anti-CMV activity. Holder pasteurization significantly reduced the antiviral activity. CONCLUSIONS: Human milk is endowed with anti-CMV activity and its potency may vary depending on the stage of lactation and the serological status of the mother. This biological property could partially neutralize CMV particles excreted in the milk of CMV IgG-positive mothers thus reducing the risk of transmitting infectious viruses to the infant.
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Anticuerpos Antivirales/análisis , Calostro/inmunología , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Leche Humana/inmunología , Adulto , Anticuerpos Antivirales/inmunología , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/transmisión , Femenino , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Recién Nacido , Recien Nacido Prematuro , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Bancos de Leche Humana , Madres , PasteurizaciónRESUMEN
BACKGROUND: Fortification of human milk is a standard practice for feeding very low birth weight infants. However, preterm infants often still experience suboptimal growth and feeding intolerance. New fortification strategies and different commercially available fortifiers have been developed. Commercially available fortifiers are constituted by a blend of ingredients from different sources, including plant oils and bovine milk proteins, thus presenting remarkable differences in the quality of macronutrients with respect to human milk. Based on the consideration that donkey milk has been suggested as a valid alternative for children allergic to cow's milk proteins, due to its biochemical similarity to human milk, we hypothesized that donkey milk could be a suitable ingredient for developing an innovative human milk fortifier. The aim of the study is to evaluate feeding tolerance, growth and clinical short and long-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk, in comparison to an analogous population fed with traditional fortifier and protein supplement containing bovine milk proteins. METHODS: The study has been designed as a randomized, controlled, single-blind clinical trial. Infants born <1500 g and <32 weeks of gestational age were randomized to receive for 21 days either a combination of control bovine milk-based multicomponent fortifier and protein supplement, or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The fortification protocol followed is the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. Weight, length and head circumference are measured; feeding tolerance is assessed by a standardized protocol. The occurrence of sepsis, necrotizing enterocolitis and adverse effects are monitored. DISCUSSION: This is the first clinical study investigating the use of a human milk fortifier derived from donkey milk for the nutrition of preterm infants. If donkey milk derived products will be shown to improve the feeding tolerance or either of the clinical, metabolic, neurological or auxological outcomes of preterm infants, it would be an absolute innovation in the field of feeding practices for preterm infants. TRIAL REGISTRATION: ISRCTN - ISRCTN70022881 .
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Alimentos Fortificados , Proteínas de la Leche/uso terapéutico , Leche Humana , Encuestas Nutricionales/estadística & datos numéricos , Estado Nutricional , Aumento de Peso/efectos de los fármacos , Animales , Equidae , Humanos , Recien Nacido Prematuro/crecimiento & desarrollo , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Italia , Proteínas de la Leche/administración & dosificación , Proyectos de InvestigaciónRESUMEN
Preterm infants fed fortified human milk (HM) in standard (STD) fashion grow slower than preterm formula fed infants. Recently, low protein intake has been proven to be the primary limiting factor responsible for this growth failure. The main reason of protein undernutrition despite fortification is that STD fortification is based on the customary assumptions about the composition of HM. However, the protein concentration of preterm HM is variable and decreases with the duration of lactation. Also, the protein concentration of banked donor milk, which is most often provided by mothers of term infants, is likely to be lower. Hence, most of the HM fed to preterm infants during the fortification period is likely to have an inadequately low protein concentration. This hypothesis has been confirmed very recently by comparing the assumed and actual protein intakes in preterm infants fed fortified HM. Novel fortification models have been devised to deal with the problem of ongoing protein undernutrition. Individualized fortification is the recommended method to optimize HM fortification. There are two models of individualization: "adjustable fortification" and "targeted fortification". Both ways are feasible and effective in improving protein intakes and growth. Adjustable fortification has the advantage of being practical and avoids excessive protein intakes.
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Alimentos Fortificados , Fenómenos Fisiológicos Nutricionales del Lactante , Recien Nacido Prematuro/crecimiento & desarrollo , Leche Humana , Proteínas en la Dieta/administración & dosificación , Electrólitos/administración & dosificación , Ingestión de Energía , Humanos , Recién Nacido , Recien Nacido Prematuro/fisiología , Leche Humana/química , Minerales/administración & dosificación , Necesidades Nutricionales , Valor NutritivoRESUMEN
A mixture of neutral short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) has been shown to reduce the incidence of atopic dermatitis (AD) and infectious episodes during the first 6 mo of life. This dual protection occurred through the intervention period. The present study evaluated if these protective effects were lasting beyond the intervention period. In a prospective, randomized, double-blind, placebo-controlled design, healthy term infants with a parental history of atopy were fed either a prebiotic-supplemented (8 g/L scGOS/lcFOS) or placebo-supplemented (8 g/L maltodextrin) hypoallergenic formula during the first 6 mo of life. Following this intervention period, blind follow-up continued until 2 y of life. Primary endpoints were cumulative incidence of allergic manifestations. Secondary endpoints were number of infectious episodes and growth. Of 152 participants, 134 infants (68 in placebo, 66 in intervention group) completed the follow-up. During this period, infants in the scGOS/lcFOS group had significantly lower incidence of allergic manifestations. Cumulative incidences for AD, recurrent wheezing, and allergic urticaria were higher in the placebo group, (27.9, 20.6, and 10.3%, respectively) than in the intervention group (13.6, 7.6, and 1.5%) (P < 0.05). Infants in the scGOS/lcFOS group had fewer episodes of physician-diagnosed overall and upper respiratory tract infections (P < 0.01), fever episodes (P < 0.00001), and fewer antibiotic prescriptions (P < 0.05). Growth was normal and similar in both groups. Early dietary intervention with oligosaccharide prebiotics has a protective effect against both allergic manifestations and infections. The observed dual protection lasting beyond the intervention period suggests that an immune modulating effect through the intestinal flora modification may be the principal mechanism of action.
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Control de Enfermedades Transmisibles , Suplementos Dietéticos , Hipersensibilidad/prevención & control , Oligosacáridos/farmacología , Probióticos/farmacología , Dieta , Método Doble Ciego , Humanos , Incidencia , Lactante , Alimentos Infantiles , Recién NacidoRESUMEN
In a prospective, double-blind, placebo-controlled trial, the efficacy and safety of ursodeoxycholic acid (UDCA) was evaluated in preterm infants, in terms of its potential impact on fat absorption, advancement of enteral feeding, development of cholestasis, growth, nutritional status, and metabolic status. Although fecal fat excretion slightly decreased and achievement of full enteral feeding was earlier in the UDCA group, these differences were not significant. Interestingly, whereas serum gamma-glutamyl transferase activity increased during the parenteral nutrition period in the placebo group, we observed a constant and significant decrease in the UDCA group. This observation warrants further investigation to determine the utility of prophylactic UDCA in preventing cholestasis in infants with prolonged parenteral nutrition.
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Colagogos y Coleréticos/uso terapéutico , Colestasis/prevención & control , Emulsiones Grasas Intravenosas , Recien Nacido Prematuro/crecimiento & desarrollo , Nutrición Parenteral Total/efectos adversos , Ácido Ursodesoxicólico/uso terapéutico , Colagogos y Coleréticos/efectos adversos , Colestasis/inducido químicamente , Método Doble Ciego , Emulsiones Grasas Intravenosas/efectos adversos , Emulsiones Grasas Intravenosas/farmacocinética , Heces/química , Femenino , Humanos , Lactante , Recién Nacido , Absorción Intestinal/efectos de los fármacos , Masculino , Estado Nutricional , Proyectos Piloto , Estudios Prospectivos , Seguridad , Resultado del Tratamiento , Ácido Ursodesoxicólico/efectos adversos , gamma-Glutamiltransferasa/metabolismoRESUMEN
A mixture of neutral short chain galactooligosaccharides and long chain fructo-oligosaccharides (scGOS/lcFOS) has been shown to have prebiotic and immunomodulatory effects comparable to human milk oligosaccharides. This can be translated into clinical practice as a potential to prevent infections and allergy. The hypothesis of this study was that this specific prebiotic mixture could have a preventive effect against infections during the first 6 mo of life. In a prospective, randomized, double-blind, placebo-controlled trial, healthy term infants with a parental history of atopy were fed either prebiotic-supplemented (8 g/L scGOS/lcFOS) or placebo-supplemented (8 g/L maltodextrin) hypoallergenic formula during the first 6 mo of life. The primary outcome measures were infectious episodes, number of infections requiring antibiotics, and incidence of infections. During the study period, infants in the scGOS/lcFOS group had fewer episodes of all types of infections combined (P = 0.01). They also tended to have fewer upper respiratory tract infection episodes (P = 0.07) and fewer infections requiring antibiotic treatment (P = 0.10). Similarly, the cumulative incidence of recurring infections was significantly lower in the scGOS/lcFOS group. The cumulative incidence of any recurring infection and recurring respiratory infections was 3.9 and 2.9% in the scGOS/lcFOS group and 13.5 and 9.6% in the placebo group, respectively (P < 0.05). Oligosaccharide prebiotics reduced the number of infectious episodes and the incidence of recurring, particularly respiratory, infections during the first 6 mo of life. Although the exact mechanism of action is under investigation, it is very likely that the immune modulating effect of this prebiotic mixture through intestinal flora modification is the principal mechanism for the observed infection prevention early in life.
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Control de Enfermedades Transmisibles , Suplementos Dietéticos , Alimentos Infantiles , Oligosacáridos/uso terapéutico , Animales , Método Doble Ciego , Humanos , Incidencia , Lactante , Recién Nacido , Infecciones/epidemiología , Leche , PlacebosRESUMEN
OBJECTIVES: Awareness of the considerable incidence of bovine protein allergy in infancy makes it necessary to eliminate cow's milk antigens from the diet in special cases. The primary objective of this review is to discuss the nutritional aspects and appropriate use of hypoallergenic formulas as a substitute for cow's milk formulas and to present new alternative feeding modalities in this field. DATA SOURCES: Related articles in PubMed (National Library of Medicine) were reviewed. This review is a synthesis of these sources along with the discussions with experts in this field and the expert opinion of the authors. RESULTS: Soy protein-based and hydrolyzed milk protein formulas are the most commonly used alternative protein sources in the case of bovine protein allergy. Despite the adequacy of their nutritional values, there are still some problems to be solved regarding these formulas. In addition, a considerable percentage of the infants with bovine protein allergy may also present allergenic reactions to soy proteins as well as to hydrolyzed milk proteins. Thus, there still exists chaos in the selection of the most appropriate formula for infants sensitized to cow's milk protein. Rice protein-based formulas, probiotics, and prebiotics are expected to be new effective alternatives. CONCLUSIONS: Bovine protein allergy constitutes an important place in childhood food allergies. Soy protein-based and hydrolyzed protein formulas have some disadvantages and risk of allergenic activity that is not to be underestimated. So, substitution of cow's milk protein with an alternative protein source in sensitized infants has become an art rather than a science. Rice protein, prebiotics, and probiotics appear to be valuable alternatives giving hope for the future.