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One of the main concerns in human milk banks (HMB) is the transmission of human cytomegalovirus (HCMV) that could be present in the milk of infected women. There are consistent data showing that this virus is destroyed by Holder pasteurization (62.5 oC for 30min), but there is a lack of information about the response of the virus to the treatment at lower temperatures in strict HMB conditions. In order to analyze the effectiveness of different temperatures of pasteurization to eliminate HCMV in human milk, a preliminary assay was performed incubating HCMV-spiked raw milk samples from donor mothers at tested temperatures in a PCR thermocycler and the viral infectivity was assayed on cell cultures. No signs of viral replication were observed after treatments at temperatures equal or greater than 53 °C for 30 min, 20 min and 10 min, 58 °C for 5 min, 59 °C for 2 min, and 60 °C for 1 min. These data were confirmed in a pasteurizer-like model introducing HCMV-spiked milk in disposable baby bottles. No viral infectivity was detected on cell cultures after heating treatment of milk for 30 min at temperatures from 56 °C to 60 °C. Thus, our results show that by using conventional pasteurization conditions, temperatures in the range of 56 oC to 60 °C are enough to inactivate HCMV. Consequently, we consider that, in order to provide a higher quality product, the current recommendation to pasteurize both mother’s own milk and donated milk at 62.5 °C must be re evaluated.

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.

Adequate nutrition is fundamental to neonatal survival and short-term outcomes, but it also has long-term consequences on quality of life and neurologic development of preterm infants. Donkey milk has been suggested as a valid alternative for children allergic to cows&rsquo, milk proteins, due to its biochemical similarity to human milk, we, hence, hypothesized that donkey milk could be a suitable basis for developing an innovative human milk fortifier for feeding preterm infants. The aim of the current study was to extend the findings and to evaluate the neurodevelopmental outcomes at 18 months of corrected age of the infants enrolled in the clinical trial named &ldquo, Fortilat&rdquo, Infants born &le, 1500 g and &lt, 32 weeks of gestational age were randomized to receive either a combination of bovine milk-based multicomponent fortifier and protein supplement or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The followed fortification protocol was the same for the two groups and the two diets were designed to be isoproteic and isocaloric. All infants enrolled were included in a developmental assessment program. The neurodevelopmental assessment was performed at 18 &plusmn, 6 months of corrected age. Minor and major neurodevelopmental impairment and General Quotient (GQ) at the Griffiths-II Mental Development Scale were considered. The GQ was considered both in continuous and as two classes: lower than and higher than (or equal to) a defined cutoff (GQcl). The difference in GQ and GQcl between the two arms was estimated using Mann&ndash, Whitney&ndash, Wilcoxon test or Fischer exact test, respectively, on the assumption of casual loss at follow-up. A further analysis was performed using generalized linear models. There were 103 children (bovine milk-derived fortifier arm = 54, donkey milk-derived fortifier arm = 49) included for the neurodevelopmental follow-up. All observations were included in the interval of 18 &plusmn, 6 months of corrected age. No significant difference was observed between the two arms in the incidence of neurologic sequelae and the GQs were similar in the two arms. Our results demonstrated no difference for the donkey milk-derived fortifier compared to standard bovine-derived fortifier regarding long-term neurodevelopmental outcomes.

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.

The purpose of the present randomized controlled clinical trial was to compare the use of donkey milk-derived fortifier (DF) with commercial bovine milk-derived fortifier (BF) in very preterm or very-low-birth-weight newborns, in terms of feeding tolerance.This trial included 156 newborns born at32 weeks of gestational age and/or with a birth weight ≤1500 g. Newborns were randomized 1:1 to receive enteral feeding with either a BF-arm, or a new, DF-arm for 21 days. The fortification protocol was the same for both study arms, and the 2 diets were designed to be isoproteic and isocaloric. Feeding tolerance was assessed by a standardized protocol.The risk of feeding intolerance tended to be lower in DF-arm than in BF-arm, with a relative risk reduction of 0.63 (95% confidence interval: -0.29, +0.90). The mean number of episodes per newborn of feeding intolerance and feeding interruptions (any duration) were consistently lower in the DF-arm than in the BF-arm. Episodes of bilious gastric residuals and vomiting were significantly lower in the DF-arm. Time needed to reach full enteral feeding (150 mL · kg · day) and daily weight increase between the first day of exclusive enteral feeding (ie, without administering intravenous fluids) and discharge were similar in the BF- and DF-arms.These results suggest that DF improve feeding tolerance when compared with standard bovine-derived fortifiers, with a similar auxological outcome.

Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk. The aim of this study was to investigate the anti-HCMV activity of human preterm colostrum and clarify the role of colostrum-derived extracellular vesicles (EVs). Preterm colostrum samples were collected and the EVs were purified and characterized. The in vitro anti-HCMV activity of both colostrum and EVs was tested against HCMV, and the viral replication step inhibited by colostrum-purified EVs was examined. We investigated the putative role EV surface proteins play in impairing HCMV infection using shaving experiments and proteomic analysis. The obtained results confirmed the antiviral action of colostrum against HCMV and demonstrated a remarkable antiviral activity of colostrum-derived EVs. Furthermore, we demonstrated that EVs impair the attachment of HCMV to cells, with EV surface proteins playing a role in mediating this action. These findings contribute to clarifying the mechanisms that underlie the protective role of human colostrum against HCMV infection.

The recent COVID‐19 pandemic has spread to Italy with heavy consequences on public health and economics. Besides the possible consequences of COVID‐19 infection on a pregnant woman and the fetus, a major concern is related to the potential effect on neonatal outcome, the appropriate management of the mother–newborn dyad, and finally the compatibility of maternal COVID‐19 infection with breastfeeding. The Italian Society on Neonatology (SIN) after reviewing the limited scientific knowledge on the compatibility of breastfeeding in the COVID‐19 mother and the available statements from Health Care Organizations has issued the following indications that have been endorsed by the Union of European Neonatal & Perinatal Societies (UENPS). If a mother previously identified as COVID‐19 positive or under investigation for COVID‐19 is asymptomatic or paucisymptomatic at delivery, rooming‐in is feasible, and direct breastfeeding is advisable, under strict measures of infection control. On the contrary, when a mother with COVID‐19 is too sick to care for the newborn, the neonate will be managed separately and fed fresh expressed breast milk, with no need to pasteurize it, as human milk is not believed to be a vehicle of COVID‐19. We recognize that this guidance might be subject to change in the future when further knowledge will be acquired about the COVID‐19 pandemic, the perinatal transmission of SARS‐CoV‐2, and clinical characteristics of cases of neonatal COVID‐19.

Human milk fortification is a routine clinical practice for feeding preterm infants. We hypothesized that donkey milk can be a suitable basis for developing an innovative human milk fortifier. Our randomized controlled single-blind clinical trial, named &ldquo, Fortilat&rdquo, evaluated the feeding tolerance, growth and clinical short-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk. The aim of the current study is to extend the previous findings and to evaluate the auxological outcomes of the infants enrolled in the &ldquo, trial at 18 months of age. In the previous trial &ldquo, the fortification protocol followed was the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. All infants enrolled in the trial were included in a premature infant developmental evaluation program consisting of hospital visits at 40 &plusmn, 1 weeks of postmenstrual age, and at 6, 12 and 18 months of corrected age. Weight, head circumference and length were expressed in z-score using neonatal Intergrowth21st and INeS charts at birth, and WHO 0&ndash, 5 years growth charts at 18 months. 122 children (Bovine-arm = 62, Donkey-arm = 60) were included in this study. All the observations were recorded in the interval of 18 &plusmn, 3 months of the correct age. The two groups did not differ for head circumference, length or weight at 18 months of age. Our data show that fortifiers derived from donkey milk had not different long term auxological outcomes of standard bovine-derived fortifier, but the new donkey milk fortifier was well tolerated in our population.

Background: Feeding intolerance is a frequent diagnosis in very preterm infants. As seen in the FortiLat trial, human milk fortification with the new donkey milk-derived human milk fortifier (DF) seems to improve feeding tolerance in these infants. The aim of this study was to evaluate the effects of using the DF compared with bovine milk-derived fortifier (BF) on gastroesophageal reflux (GER) in very low birth weight (VLBW) infants. Methods: Over a total of 156 preterm infants were enrolled into the FortiLat trial (GA &lt, 32 weeks and birth weight &lt, 1500 g) and randomized into the BF arm or DF arm, and we selected all infants with clinical signs of GER and cardiorespiratory (CR) symptoms. All the infants underwent CR and multichannel intraluminal impedance and pH (MII/pH) monitoring associated with gastric ultrasound to evaluate GER and gastric emptying time. Results: 10 infants were enrolled, and 5 were in the DF arm. At MII/pH, infants enrolled into the DF arm showed a lower GER frequency than BF arm infants (p = 0.036). Half gastric emptying time was similar in DF and BF arm infants (p = 0.744). Conclusion: The use of donkey-derived human milk fortifier reduced the GER frequency and consequently should be recommended in infants with feeding intolerance.

Introduction: Knowledge about how a lactating woman's diet influences the composition of her breast milk is still very limited. In particular, no study has evaluated the role of adherence to the Mediterranean diet on human milk characteristics. Aim: We carried out an observational study to investigate the influence of mother adherence to a Mediterranean diet on her breast milk composition. Methods: Between 2012 and 2014, 300 healthy mothers, who exclusively breastfed their babies, were enrolled from five centers across Italy. During a visit to the hospital center 6 weeks after childbirth these women were asked to provide a sample of their freshly expressed breast milk and to answer a series of questions on personal characteristics and lifestyle factors. The application of a validated food frequency questionnaire allowed the collection of detailed dietary habits. Milk was collected and then stored until chemical analyses were performed. The study has been registered (Trial Registration: Dutch Trial register NTR3468). Descriptive analyses on baseline characteristics of mothers and babies were carried out on the participants, overall and stratified by center. Results: The participants had a mean age of 33 years (SD = 4.06), and a pre-pregnancy BMI of 22.3 Kg/m2 (SD = 3.22). Forty-seven percent gave birth to their first child, 40% to the second 13% to the third or subsequent child. Babies had a mean birth weight of 3,324 g (DS = 389), and a mean length of 51 cm (SD = 1.94). Fifty-three percent were males. Conclusion: The present work provides the general description and the characteristics of mothers and babies included in the MediDiet study.

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 VLBWinfants. 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., The authors thank the Italian Association of Human Milk Banks (Associazione Italiana Banche del Latte Umano Donato = AIBLUD) for its continuous efforts to promote research in the field of donor human milk and human milk banks, and for the financial support given to the publication of this manuscript.

Background: A mother's own milk (MOM) is the gold standard for the feeding and nutrition of preterrn and full term infants. When MOM is not available or there is not enough, donor human milk (DHM) should be used. Milk delivered to Human Milk Banks (HMBs) should be pasteurized to inactivate viral and bacterial agents. Currently, a pasteurization process at 62.5 degrees C for 30 min (Holder pasteurization, HoP) is recommended in all international HMBs guidelines. State of the art: It is known that HoP affects some of the nutritional and biological components of human milk. Studies have demonstrated that temperature cycle in HoP is not always controlled or calibrated. A better check of these parameters in the pasteurizers on the market today may contribute to an improvement of the quality of HM, still maintaining some of the negative effects of the heat treatment of human milk. So, food industry, and dairy industry in particular, are evaluating innovative methodologies alternative to HoP to better preserve the nutritional and biological properties of fresh human milk, while assuring at least the same microbiological safety of HoP. The most studied processing techniques include High-Temperature-Short-Time (HTST) pasteurization, High Pressure Processing (HPP), and Ultraviolet-C (UV-C) irradiation. HTST is a thermal process in which milk is forced between plates or pipes that are heated on the outside by hot water at a temperature of 72 degrees C for 5-15 s. HPP is a non-thermal processing method that can be applied to solid and liquid foods. This technology inactivates pathogenic microorganisms by applying a high hydrostatic pressure (usually 300-800 MPa) during short-term treatments (, The authors are grateful to the Italian Association of Human Milk Banks (Associazione Italiana Banche del Latte Umano Donato = AIBLUD) for its continuous efforts to promote research in the field of donor human milk and Human Milk Banks, and for the financial support for the publication of this manuscript.

Background: In the latest decades some compelling evidence confirmed the substantial benefits of using human milk, especially for preterm infants [1-5]. Donor human milk is a valid alternative. Objective: This survey aimed to evaluate the activity of the human milk banks in Italy, analysing several items. Methods: The Italian Association of Donor Human Milk Banks (Associazione Italiana Banche del Latte Umano Donato, AIBLUD) was founded in 2005. It currently consists of 35 human milk banks (Figure 1), whose management should follow the Italian Guidelines. Among the goals of the association, scientific work plays a major role. After publication of the Italian Guidelines, the 2012 survey on Italian human milk banks also led to a nationwide improvement: some banks were established, others that were considered inactive were shut down [11]. In 2013 the Italian Ministry of Health published the national recommendations, based on the Italian Guidelines [12]. Results: 91% of the banks (32/35) responded to this second survey. Table 2 shows the average number of hours per week dedicated to the milk bank activity. This data varies greatly among the banks, as it did in 2012. The majority of the banks keeps having approximately 6 hours a day of work Conclusion: This second survey gave AIBLUD and the Italian Ministry of Health important information on the Italian human milk banks, overcoming their difficulties and correcting some negative aspects.

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.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.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.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.

Holder pasteurization (62.5 degrees C for 30 min) is recommended by all international human milk bank guidelines to prevent infections potentially transmitted by donor human milk. A drawback is that it affects some human milk bioactive and nutritive components. Recently, High Temperature-Short Time (HTST) pasteurization has been reported to be a valuable alternative technology to increase the retention of some biological features of human milk. Nevertheless, to date, few data are available about the impact of pasteurization methods other than Holder on the antiviral activity of human milk. The present study was aimed at evaluating the antiviral activity of human milk against a panel of viral pathogens common in newborns and children (i.e., herpes simplex virus 1 and 2, cytomegalovirus, respiratory syncytial virus, rotavirus, and rhinovirus), and at assessing the effect of Holder and HTST pasteurization on milk's antiviral properties. The results indicate that human milk is endowed with antiviral activity against all viruses tested, although to a different extent. Unlike the Holder pasteurization, HTST preserved the inhibitory activity against cytomegalovirus, respiratory syncytial virus, rotavirus and herpes simplex virus type 2. By contrast, both methods reduced significantly the antiviral activities against rhinovirus and herpes simplex virus type 1. Unexpectedly, Holder pasteurization improved milk's anti-rotavirus activity. In conclusion, this study contributes to the definition of the pasteurization method that allows the best compromise between microbiological safety and biological quality of the donor human milk: HTST pasteurization preserved milk antiviral activity better than Holder.

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. The study has been designed as a randomized, controlled, single-blind clinical trial. Infants born

Pasteurization, performed at 62.5°C for 30 minutes (holder pasteurization), is currently recommended in all international human milk banks guidelines, but it affects some human milk bioactive and nutritive components. The present systematic review is aimed at critically reviewing evidence on the suitability of human milk processing techniques other than holder pasteurization, both thermal and nonthermal, to ensure microbiological safety, and on the effects of these techniques on biologically active donor milk components. A systematic review of English and non-English articles using Medline, PubMed, Embase, SCOPUS, and CAB Abstracts, with no restriction in publication date was performed. Search terms included: human, breast, donor, or banked milk, breastmilk, breast fed, breastfed, breastfeed; HTST, Flash, High Pressure, UV, ultrasonic or nonthermal; process, pasteuris, pasteuriz. Only primary research articles published in peer-reviewed journals were included, providing or not a comparison with holder pasteurized human milk, provided that the pasteurization technique was clearly described, and not intended for domestic use. Additional studies were identified by searching bibliographies of relevant articles. Twenty-six studies were identified as being relevant. Two examined both High Pressure Processing and High-Temperature-Short-Time pasteurization; 10 only examined High Pressure Processing; 10 only examined High-Temperature-Short-Time; 2 articles examined ultraviolet irradiation; 2 articles examined (thermo-)ultrasonic processing. The results indicate that data about safety for microbiological control are still scarce for most of the novel technologies, and that consensus on processing conditions is necessary for nonthermal technologies, before any conclusions on the qualitative and nutritional advantages of these techniques can be drawn.

The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding tolerance and with reduced cardiovascular risk factors during adolescence. Presence of a human milk bank (HMB) does not decrease breast-feeding rates at discharge, but decreases the use of formula during the first weeks of life. This commentary emphasizes that fresh own mother's milk (OMM) is the first choice in preterm infant feeding and strong efforts should be made to promote lactation. When OMM is not available, DHM is the recommended alternative. When neither OMM nor DHM is available, preterm formula should be used. DHM should be provided from an established HMB, which follows specific safety guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment ; on the optimization of HM fortification ; and on further evaluation of the potential clinical benefits of processed and fortified DHM.

Background Organization of the sleep states and a normal sleep pattern in the neonatal period and early infancy is essential for brain development and plasticity. The establishment of a consolidated circadian sleep-wake cycle occurs between 1 and 4 months of life in term infants. This period may be even longer for preterm infants who are exposed to relentless interventions in neonatal intensive care units. The sleep should be respected and protected. Objective and methods Human milk (HM) contains bioactive sleep-promoting components, and recent evidence shows that some of these components show circadian oscillations. This article reviews the existing evidence regarding the role of these HM components on sleep. This topic is prefaced with a brief information about the basic concepts concerning sleep. Consecutively, chronobiotic and chrononutrition concepts are introduced. Results Melatonin, tryptophan, nucleosides/nucleotides, and vitamin B12 are components of HM that have sleep-promoting characteristics. The sleep-inducing effects of these components are well-established in animal and adult human studies. Interestingly, melatonin, tryptophan, and 5′-adenosine monophosphate and 5′-guanosine monophosphate nucleotides in HM have been shown to exhibit also circadian oscillations. Although 5′-uridine monophosphate does not have a circadian rhythm, its levels increase during the night. Conclusion HM has a potential to function as a “synchronizer,” helping the infant to consolidate a circadian sleep-wake cycle, thanks to its several bioactive components with chronobiotic characteristics. Research is warranted to address gaps in this field, such as the association between the circadian oscillations of the sleep-promoting factors in HM and the quantity/quality of infant sleep.

To cite this article: Schouten B, Van Esch BCAM, Kormelink TG, Moro GE, Arslanoglu S, Boehm G, Knippels LMJ, Redegeld FA, Willemsen LEM, Garssen J. Non-digestible oligosaccharides reduce immunoglobulin free light-chain concentrations in infants at risk for allergy. Pediatr Allergy Immunol 2011; 22: 537–542. Abstract Prebiotic oligosaccharides influence the intestinal microbiota and can positively modulate the infant’s immune system. It was demonstrated that a special prebiotic mixture (Immunofortis®) of short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS) can reduce the cumulative incidence of atopic dermatitis (AD) in infants at risk for allergy as determined using the AD symptom score (SCORAD). Additionally, it was shown very recently that immunoglobulin free light-chain (Ig-fLC) might be involved in the pathophysiology of allergic disease. Increased Ig-fLC concentrations were found in patients suffering from AD, cow’s milk allergy, allergic rhinitis, or asthma. In this study, the effect of supplementation of scGOS/lcFOS on the Ig-fLC plasma concentrations in infants at risk for allergy was assessed. The plasma kappa and lambda Ig-fLC concentrations were measured in a double-blind, placebo-controlled, randomized trial, in which infants at risk for developing allergic disease received a hypoallergenic whey formula containing 8 g/l of the scGOS/lcFOS mixture (n = 34) or maltodextrin as a placebo (n = 40) for 6 months. After intervention, plasma samples were collected, and total plasma concentrations of lambda and kappa Ig-fLC were analyzed using ELISA. Total kappa and lambda Ig-fLC plasma concentrations were higher in infants suffering from AD when compared to infants without any sign of AD. In infants receiving the prebiotic mixture, the Ig-fLC levels were significantly lower compared to the placebo-fed infants (p

Over the last decades, significant progress in the fields of perinatal and neonatal medicine has resulted in improved survival of very low and extremely low-birth weight infants. At present, these ...

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.

The vaccine response to poliovirus, diphtheria and tetanus toxoids in relation to protein intake was studied in infants, either breast-fed or given low (1.1 g/100 ml) or conventional (1.5 g/100 ml) protein formula. Serum, saliva and faeces antibodies were measured by the enzyme-linked immunosorbent assay. Neutralizing poliovirus antibodies were determined. The serum, saliva and faeces antibody responses in the two formula-fed groups of infants did not differ significantly, but for the low protein formula group which had significantly higher serum neutralizing titres to poliovirus after the second vaccine dose than the conventional formula group. However, the breast-fed group had significantly higher antibody levels than the two formula-fed groups together: serum IgG to diphtheria toxoid (p less than 0.01) and serum neutralization of poliovirus (p less than 0.001) at 21-40 months of age, saliva secretory IgA to tetanus (p less than 0.01), diphtheria toxoid (p less than 0.01) and poliovirus (p less than 0.05), as well as faecal IgM to tetanus toxoid (p less than 0.05) and poliovirus (p less than 0.01 and p less than 0.05) at 3 and 4 months of age. Breast-fed infants thus showed better serum and secretory responses to peroral and parenteral vaccines than the formula-fed, whether with a conventional or low protein content.

A new small-scale continuous-flow High-Temperature Short-Time (HTST) pasteurizer has been designed for treating human milk. The efficacy of the new HTST device was assessed on inoculated Listeria monocytogenes, Staphylococcus aureus and Chronobacter sakazakii, as well as on raw human milk bacteria. The milk biochemical quality after HTST pasteurization was assessed in comparison to a standard Holder pasteurization, by determining the secretory IgAs (sIgAs) content, the protein profile, lysozyme and the Bile Salt Stimulated Lipase (BSSL) activities. No pathogen or bacterial growth was detected after HTST pasteurization with the new instrument. Changes in the protein profile were observed in the milk pasteurized according to both processes. The sIgAs content and BSSL activity were significantly higher in the milk pasteurized with the new device than in the same milk treated by the standard Holder pasteurization. In conclusion, the new HTST apparatus: (i) can effectively pasteurize human milk with a better retention of sIgAs content and BSSL activity; (ii) comply to human milk banking safety requirements. Industrial relevance Currently, 210 active human milk banks are located in Europe (and 17 more are planned). The majority of the European banks still use Holder-based pasteurizers, which, despite efficacy in ensuring microbiological safety, are known to reduce/disrupt important nutritional and non-nutritional biological factors. Although already widely established in food industry, the advantages of HTST technology were tested only at small laboratory scale for human milk. The device tested in the present research was specifically designed to provide human milk banks with the technology they need to ensure a safe and lower-impact pasteurization process, that is suitable for processing different volumes of donations. The device can pasteurize up to 10 L of milk per hour, with a minimum volume of 100 mL. The system is designed to be cleaned-in-place (CIP) after each pasteurization run and sanitized immediately prior to the next use, being thus more suitable for treating pools of milk from different donors than milk from single donations. Italian and EU patents have been filed for the device, within a partnership between public research institutions, stakeholders (Italian association of donor milk banks), and a private company in the sector of dairy processing equipment. The device has achieved a Technology Readiness Level (TRL) 6 (Prototype demonstration in a relevant environment). The cost of the new device will be comparable to that of a typical human milk Holder pasteurizer.

Awareness of the key role of the intestinal microflora in the generation of the immunophysiological regulation and in the defence against pathogenic agents has attracted our interest in ways of manipulating the microbiota to improve health. Dietary modulation of the intestinal microflora is today one of the main topics of interest in the nutritional sciences. Performing this modulation in the neonatal or early infancy period, when immunological programming takes place, is a relatively new concept. Fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) are prebiotics whose bifidogenic activity has been proven in adults. However, only recently have they been combined in infant formulas to reproduce the prebiotic effect of human milk oligosaccharides. In two consecutive trials, it has been demonstrated that supplementation of infant formulas with a mixture of GOS and FOS modified the fecal flora of term and preterm infants, stimulating the growth of Bifidobacteria. In the trial with term infants, the bifidogenic effect of the prebiotic mixture was dose dependent and there was also a significant increase in the number of Lactobacilli in the supplemented group. These findings offer a promising horizon for the early prevention of allergy and infections in infants.

Hypogalactia has a relative high frequency in women having delivered preterm infants, who often have difficulties in maintaining a sufficient production of milk for their infants’ needs over prolonged periods of time. Recent studies have shown a potential galactogogue effect of silymarin on milk production in animal models (cows and rats) and in humans (mothers of term newborns); nonetheless, none of the studies conducted on humans consisted of double-blind randomized clinical trials and no data are available concerning mothers who delivered preterm infants. The aim of our study was to assess the efficacy of silymarin (BIO-C®) as galactogogue and its tolerability in mothers who delivered preterm infants. We enrolled 50 mothers at 10±1 days post-partum who had delivered infants at ® and placebo arms. No adverse events were observed in the 2 arms among mothers and infants, and silymarin and its metabolites were not detectable in the analyzed human milk samples. Further investigation on specific patient groups affected by hypogalactia, defined according to stricter criteria, should be planned to assess the efficacy of the product in increasing milk production.

Inadequate nutrition leading to growth failure is common among premature infants. Although fortified breast milk (breast milk plus commercially prepared fortifier) is the preferred feeding, nutrient intakes achieved with fortified breast milk fall short of meeting nutrient needs. This is mainly due to inadequate protein content of fortifiers and variability in composition of expressed breast milk.A new adjustable fortification regimen has been designed to ensure that protein needs of premature infants are met at all times. The new regimen encompasses increasing the amount of fortifier and adding extra protein to breast milk guided by periodic determinations of blood urea nitrogen (BUN). The study tested the hypothesis that infants fed according to the new regimen have higher protein intakes and improved weight gain compared to infants fed according to standard fortification regimen.In a prospective, controlled trial, preterm infants with birth weights of 600-1750 g and gestational ages between 26 and 34 weeks were fed their own mother's milk or banked donor milk or both. Infants were randomly assigned before 21 days of age to either the new adjustable fortification regimen or the standard regimen. The study period began when feeding volume reached 150 ml/kg/day and ended when infants reached a weight of 2000 g. Standard fortification (STD) consisted in the use of the recommended amount of fortifier. Adjustable fortification (ADJ) consisted in the use, in addition to standard fortification, of extra fortifier and supplemental protein guided by twice-weekly BUN determinations. The primary outcome was weight gain, with serum biochemical indicators and nutrient intakes as secondary outcomes.Thirty-two infants completed the study as planned (16 ADJ, 16 STD). Infants receiving the ADJ regimen had mean protein intakes of 2.9, 3.2 and 3.4 g/kg/day, respectively, in weeks 1, 2 and 3, whereas infants receiving the STD regimen had intakes of 2.9, 2.9, 2.8 g/kg/day, respectively. Infants on the ADJ regimen showed significantly greater gain in weight (17.5+/-3.0 vs 14.4+/-3.0 g/kg/day, P0.01) and greater gain in head circumference (1.4+/-0.3 vs 1.0+/-0.3; P0.05) than infants on the STD regimen. Weight and head circumference gain were significantly (P0.05) correlated with protein intake. No significant correlations were found between growth parameters and intake of fat and energy. There were no significant differences between groups in BUN and other serum chemical values. In the ADJ group, BUN concentrations increased significantly (P0.001) over time but were not significantly higher than in the STD group.Premature infants managed with the new adjustable fortification regimen had significantly higher weight and head circumference gains than infants managed with standard fortification. Higher protein intake appears to have been primarily responsible for the improved growth with the adjustable regimen. The new fortification method could be a solution to the problem of protein undernutrition among premature infants fed human milk.

OBJECTIVE: To evaluate the potential role of quantitative ultrasound (QUS) investigation in assessing the osteopenia of prematurity. DESIGN: QUS parameters measured at the time of discharge were related to the anthropometric characteristics and age (postnatal and gestational) of 51 (34 female and 17 male) preterm infants fed fortified human milk. METHODS: QUS evaluation was performed at the humerus (h) by measuring two parameters: ultrasound velocity (hSOS, in m/s) and bone transmission time (hBTT, in micros). A group of 43 term infants (29 female and 14 male) was also evaluated. RESULTS: In preterm infants, significant correlations were found for hSOS and hBTT vs gestational age (r=0.504, 0.477, P

Human milk confers health benefits of vital importance for the sick and preterm infants in neonatal intensive care units (NICUs). Mother’s own milk is the first choice in preterm infant feeding, and every effort should be made to promote lactation. When mother’s milk is not available or is insufficient, donor human milk (DHM) is recommended. Yet, occasionally, the concern that the use of DHM might decrease breastfeeding is being raised. The present data collection planned by the Italian Association of Human Milk Banks (AIBLUD) in collaboration with the Italian Neonatal Network (INN) attempted to address this concern. A total of 4277 very low birth weight (VLBW) infants from 83 Italian NICUs were evaluated for this comparative analysis. The 83 Italian NICUs were divided into two groups: centers with a human milk bank (HMB) and centers without a HMB; the available parameters in the network – “any and exclusive breastfeeding rates” and “exclusive formula rate” at discharge – were compared. Exclusive breastfeeding rate at discharge was significantly higher in NICUs with a HMB than in NICUs without (29.6% vs. 16.0%, respectively). Any breastfeeding rate at discharge tended to be higher in the NICUs with HMB (60.4% vs. 52.8%, P=0.09), and exclusive formula rate was lower in the NICUs with HMB (26.5% vs. 31.3%), but this difference was not significant. This report shows that the presence of a HMB and the use of DHM in NICU are associated with increased breastfeeding rate at discharge from the hospital for VLBW infants.

The benefits of human milk for preterm infants are mainly the result of its nutritional characteristics and the presence of biologically active compounds. Among these compounds, glycosaminoglycans (GAGs) play an emerging leading role. When mother's milk is unavailable or in short supply, pasteurised donor milk represents an important nutritional alternative. The aim of this study was to evaluate the effect of Holder pasteurisation on the concentration of different GAGs in preterm human milk.Milk samples collected from 9 mothers having delivered preterm were divided into 2 parts. One part of each sample was immediately frozen (-80°C), whereas the other part was pasteurised with the Holder method before being frozen at -80°C. Specific analytical procedures were applied to evaluate the amount, composition, and structure of main human milk GAGs.No significative differences were measured between not-treated and pasteurised samples for total GAGs content, relative percentages of chondroitin sulfate and heparan sulfate, and main parameters related to galactosaminoglycans structure, even if a slight decrease of total GAGs content of ∼18% was observed in treated samples.Our results indicate that the Holder pasteurisation does not significatively affect the concentration of the main human milk GAGs.

Protein quality of breast milk is superior to that of formula proteins. To ensure that the protein intake is sufficient, starter formulas with conventional protein composition provide a protein/energy ratio of 2.2-2.5 g per 100 kcal to infants, which is much higher than that supplied with breast milk. Several studies have shown that formula-fed infants have higher plasma or serum urea concentrations than breast-fed infants do. We tested if feeding formulas with improved protein quality and a protein content corresponding to the minimum level that is consistent with international recommendations (1.8 g/100 kcal) allows patients to achieve normal growth and plasma urea concentrations.Healthy term infants were enrolled into the study and were either breast-fed or randomly assigned to three formula-fed groups. Formula-fed infants received either a standard formula with a protein/energy ratio of 2.2 g/100 kcal, whereas the two other groups received formulas with a protein/energy ratio of 1.8g/100 kcal differing mainly by their source of protein. Subjects received breast milk or these formulas ad libitum as the sole source of energy from birth to four months of age in a controlled blind design (except for the breast-fed group). Anthropometric measurements (body weight and length) were obtained at birth, at 30, 60, 90, and 120 days. Energy and protein intakes were calculated from three-day dietary records. Blood was collected for biochemical measurements at 30, 60, and 120 days.No differences were found between the four feeding groups for weight- and length-gains or for body mass indices (BMI). No differences in energy intakes between the formula-fed groups could be found, whereas protein intakes were less in infants fed the 1.8 g/100 kcal formulas. Plasma urea levels of the infants fed the 1.8 g/100 kcal formulas were closer to those found in the breast-fed infants.Improvement of the amino acid profile permits a whey predominant starter formula with 1.8 g protein per 100 kcal to meet the needs of normal term infants during the first four months of life.

Background: At present, the Italian Association of Donor Human Milk Banks (Associazione Italiana Banche del Latte Umano Donato, AIBLUD) consists of 31 milk banks, whose management is based on Italian Guidelines. In 2013, AIBLUD performed a systematic survey to collect data on the activities of banks operating in Italy in the years previous to this date. Objective: The purpose of this survey was to evaluate the operational procedures of Italian Human Milk Banks in order to identify both areas of strength and room for improvement. Methods: A questionnaire was utilized to obtain national data from the 28 banks active in the year 2012 in order to evaluate the number of donors, volume of human milk collected, and other information relating to the period 2007 to 2012. Results: In all, 89% of the banks (25/28) responded to the survey. Data received primarily concerned the number of donors, volume of milk collected, and average amount of milk from each donor in the period 2007 to 2012. It was evident that in 2012 human milk banks collected a higher volume of milk than in 2007. Further, the average amount of milk from each donor was higher. Most of the milk banks were following the Italian Guidelines for traceability, control of donors, bacteriological checks, method of pasteurization, storage, thawing, type of containers, and utilization of the Hazard Analysis and Critical Control Points system. Conclusion: This survey identified both areas of strength and room for improvement in the Italian human milk banks.

To improve the nutritional management of pre-term infants, a new individualized human milk fortification system based on presupplementation milk protein analyses was evaluated.In an open, prospective, randomized multicenter study, 32 healthy preterm infants (birth weights, 920-1750 g) were enrolled at a mean of 21 days of age (range, 9-36 days) when tolerating exclusive enteral feedings of 150 ml/kg per day. All infants were fed human milk and were randomly allocated to fortification with a bovine whey protein fortifier (n = 16) or ultrafiltrated human milk protein (n = 16). All human milk was analyzed for protein content before fortification with the goal of a daily protein intake of 3.5 g/kg. During the study period (mean, 24 days) daily aliquots of the fortified milk were obtained for subsequent analyses of the protein content.Both fortifiers were well tolerated, and growth gain in weight, length, and head circumference, as well as final preprandial concentrations of serum urea, transthyretin, transferrin, and albumin were similar in both groups. The ultimate estimated protein intake was equivalent in both groups (mean 3.1+/-0.1 g/kg per day). Serum amino acid profiles were similar in both feeding groups, except for threonine (significantly higher in the bovine fortifier group) and proline and ornithine (significantly higher in the human milk protein group).Protein analyses of the milk before individual fortification provides a new tool for an individualized feeding system of the preterm infant. The bovine whey protein fortifier attained biochemical and growth results similar to those found in infants fed human milk protein exclusively with the corresponding protein intakes.

The study was aimed at evaluating the effect of prolonged refrigeration of fresh human milk (HM) on its fatty acid profile, free fatty acid content, lipase activities, and oxidative status.HM from mothers of preterm newborns was collected, pooled, and placed in the neonatal intensive care unit (NICU) refrigerator. Pooled milk was aliquoted and analyzed within 3 hours of collection, and after 24, 48, 72, and 96 hours of storage. The milk samples were analyzed for pH, total and free fatty acid profile, lipase activity at room temperature and at 4°C, lipase activity at room temperature in presence of sodium cholate (bile salt-dependent lipase), total antioxidant capacity, thiobarbituric acid reactive species, malondialdehyde, and conjugated diene concentration. The experiment was replicated in 3 independent trials.Prolonged refrigeration did not affect the fatty acid composition of breast milk, and preserved both its overall oxidative status and the activity of HM lipolytic enzymes. In particular, bile salt-dependent lipase activity, long-chain polyunsaturated fatty acids, and medium-chain saturated fatty acid concentrations were unaffected for up to 96 hours of refrigerated storage.Prolonged refrigeration of fresh HM for 96 hours maintained its overall lipid composition. The limited lipolysis during storage should be ascribed to the activity of lipoprotein lipase, responsible for the decrease in pH. Our study demonstrates that infants who receive expressed milk stored for up to 96 hours receive essentially the same supply of fatty acids and active lipases as do infants fed directly at the breast.

Human milk fed to very-low-birth-weight infants must be fortified with protein, minerals, and vitamins. We tested a new fortification regimen in which the amount of fortifier was adjusted on the basis of frequent determinations of serum urea nitrogen (SUN). A newly formulated fortifier based on bovine milk proteins was employed either in the new fashion (regimen ADJ) or in the conventional fixed proportion (regimen FIX). Using the fixed proportion, the study also compared the new fortifier with a fortifier based on human milk protein (regimen HMP). Twelve infants were studied with each of the three regimens; nearly all completed 3 weeks of study. Protein intake was generally higher in ADJ than FIX; the difference was significant (p < 0.01) during week 2. Weight gain was somewhat (but not significantly) greater in regimen ADJ (32.3 g/d or 18.8 g/kg/d) than in regimen FIX (30.0 g/d or 18.3 g/kg/d). SUN was higher in ADJ than in FIX, and several other serum chemical values (calcium, phosphorus, potassium) tended to be higher, probably reflecting higher intakes of these nutrients with ADJ than with FIX. Plasma concentrations of several amino acids were higher in ADJ than FIX, but none, including threonine, were outside the physiological range. In comparing regimen FIX to regimen HMP, infants on FIX received similar intakes of protein and showed slightly but not significantly more rapid weight gain. Concentrations of SUN were lower with FIX, but other serum chemical values, including amino acids, were generally similar to HMP. We conclude that use of the new adjustable fortification regimen is feasible and safe and that it should be studied further. It produced the expected increases in nutrient intakes and growth. The new bovine milk-based fortifier appears to be equivalent to the human milk-based fortifier.