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Objectives Standard of care sepsis biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) can be affected by several perinatal factors, among which perinatal asphyxia (PA) has a significant role. In this light, new early sepsis biomarkers such as presepsin (P-SEP) are needed to enact therapeutic strategies at a stage when clinical and laboratory patterns are still silent or unavailable. We aimed at investigating the potential effects of PA on longitudinal P-SEP urine levels. Methods We conducted an observational case-control study in 76 term infants, 38 with PA and 38 controls. Standard clinical, laboratory, radiological monitoring procedures and P-SEP urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Results Higher (p0.05, for all) at T0 were observed between groups. P-SEP urine levels were higher (p0.05) at 48 and 96 h were observed. No significant correlations were found (p>0.05) between P-SEP and urea (R=0.11) and creatinine (R=0.02) blood levels, respectively. Conclusions The present results, showed that PA effects on P-SEP were limited up to the first 24 h following birth in absence of any kidney function bias. Data open the way to further investigations aimed at validating P-SEP assessment in non-invasive biological fluids as a reliable tool for early EOS and LOS detection in high-risk infants.

In the history of the world, the donkey has always had a special place next to humans since the time of its domestication, about 10,000 years ago [...]

Multiple sclerosis does not seem to adversely affect fetal and neonatal outcomes, although some studies reported a possible reduction in mean birth weight and length, and a higher incidence of preterm delivery, mainly in relation to the exposure to disease-modifying drugs (DMDs) during pregnancy. Few data are available on intrauterine fetal growth and postnatal somatic development of newborns from mothers with multiple sclerosis compared to those from healthy women. For these reasons, we decided to investigate fetal growth, neonatal anthropometric parameters, and postnatal somatic development up to 12 months of life in offsprings from MS mothers.This retrospective cohort study included 211 women with multiple sclerosis, and 384 healthy women paired for maternal age and parity as controls. Fetal biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) measured during the third trimester of pregnancy (30-34 weeks' gestation) were retrieved from the computerized database of the Department (EcoPlus*) where the results of ultrasound exams performed in the hospital are stored. Newborn measurements (weight, length and head circumference) at birth were obtained from the hospital's computerized obstetric and neonatal database (Trackare* and Remote* data base); measurements at 6 and 12 months of life were obtained from the regional database (ECWMED*) of family pediatricians of our region.No differences between the two groups were observed for all the fetal parameters considered, expressed as centiles of growth according to gestational age (biparietal diameter: p = 0.40; head circumference: p = 0.40; abdominal circumference: p = 0.32; femur length: p = 0.32). No differences in gestational age at delivery, birthweight, and in the incidence of low birthweight and small for gestational age newborns were observed between the two groups. In the multiple sclerosis group a significantly higher incidence of caesarean section (p = 0.01) and late preterm delivery (at less than 37 weeks'gestation, p = 0.001) were registered. The trends of postnatal growth in weight (F = 0.53; p-value = 0.590) and length (F = 0.44; p-value = 0.645) were superimposable between the two groups. The trends of growth for head circumference showed a slightly, not significantly greater head circumference of infants from mothers with multiple sclerosis at 6 months of life, but the values at twelve months of life in the two groups were similar (F = 0.85; p-value = 0.427) . Moreover, the trends of postnatal increase of weight (F = 1.016; p-value = 0.331), length (F = 2.001; p-value = 0.146) and head circumference (F = 1.591; p-value = 0.212) of newborns/infants (from birth to twelve months of life) born to mothers with multiple sclerosis who breastfed, mothers who did not, and in the control group were similar.Multiple sclerosis in pregnancy does not seem to affect fetal growth and postnatal development during the first year of the offspring life. We think that these results represent an important and reassuring information to provide the patients with during preconception counseling.

Background Non-invasive ventilation (NIV) has been recommended as the best respiratory support for preterm infants with respiratory distress syndrome (RDS). However, the best NIV technique to be used as first intention in RDS management has not yet been established. Nasal intermittent positive pressure ventilation (NIPPV) may be synchronized (SNIPPV) or non-synchronized to the infant’s breathing efforts. The aim of the study is to evaluate the short-term effects of SNIPPV vs. NIPPV on the cardiorespiratory events, trying to identify the best ventilation modality for preterm infants at their first approach to NIV ventilation support. Methods An unmasked randomized crossover study with three treatment phases was designed. All newborn infants During the whole duration of the study, the patient’s cardiorespiratory data and data from the ventilator will be simultaneously recorded using a polygraph connected to a computer. The primary outcome is the frequency of episodes of oxygen desaturation. Secondary outcomes are the number of the cardiorespiratory events, FiO2 necessity, newborn pain score evaluation, synchronization index, and thoracoabdominal asynchrony. The calculated sample size was of 30 patients. Discussion It is known that NIPPV produces a percentage of ineffective acts due to asynchronies between the ventilator and the infant’s breaths. On the other hand, an ineffective synchronization could increase work of breathing. Our hypothesis is that an efficient synchronization could reduce the respiratory work and increase the volume per minute exchanged without interfering with the natural respiratory rhythm of the patient with RDS. The results of this study will allow us to evaluate the effectiveness of the synchronization, demonstrating whether SNIPPV is the most effective non-invasive ventilation mode in preterm infants with RDS at their first approach to NIV ventilation. Trial registration ClinicalTrials.gov NCT03289936. Registered on September 21, 2017.

The Academy of Breastfeeding Medicine published a clinical protocol for Human Milk storage, recommending refrigeration at a temperature of 4 °C up to 4 d as the optimal conditions for the safety and bactericidal capacity of Human Milk. However, few studies were conducted to evaluate the change in milk composition during this type of refrigeration storage.To elucidate some uncertainties regarding the Human Milk composition and prolonged cold storage, we have investigated the effects of storage at 4 °C up to 96 h on an important category of oxidative stress markers: the Isoprostanes (F2-isoprostanes, F4-neuroprostanes and F3-isoprostanes).The experiment was repeated 3 times to ensure reproducibility of the results. We enrolled 3 donating healthy mothers for each time (total: 9 mothers). Milk was collected with standard extraction methods. Immediately after collection, each Human Milk sample from each mother was pooled and then divided into 5 aliquots. One aliquot (0 h) was immediately frozen at -80 °C until the analysis. The other aliquots (24 h, 48 h, 72 h, 96 h) were stored in a refrigerator at 4 °C respectively for 24, 48, 72 and 96 h, then immediately frozen at -80 °C until the analysis. Milk samples were then used to determine concentration of Isoprostanes in Liquid Chromatography - Mass Spectrometry and Liquid Chromatography - Tandem Mass Spectrometry.Isoprostanes were detectable in all Human Milk samples. There was no significant trend of the concentration of the tested analytes over time.This study provides evidence of the presence in human milk of all the tested isoprostanes: in particular, F2-isoprostanes, F4-neuroprostanes and F3-isoprostanes. Refrigeration and storage of fresh Human Milk in controlled conditions for 96 h did not significantly affect its bioactivity and nutritional quality related with these biomarkers.

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.

Background: ExtraUterine Growth Restriction (EUGR) is a common definition for in-hospital growth failure of very preterm infants. Wide heterogeneity is found in definitions and anthropometric charts used to describe EUGR.Aim: We aim to compare two traditional definitions of EUGR with a newly proposed one, based on a longitudinal evaluation, that takes into account the physiological period of fluid loss after birth. We also wish to detect which definition could better predict neurodevelopmental impairment at 24 months of corrected age (CA).Methods: A total of 195 infants with GA < 30 were included. EUGR was calculated both for weight and head circumference (HC). Cross-sectional EUGR was defined as measurements < 10th percentile at discharge; longitudinal EUGR was defined as Δz-score < −1 between birth and discharge measurements. The new longitudinal “post-loss” EUGR definition was proposed as Δz-score < −1 between measurements taken at 14–21 days of life and at discharge. Longitudinal postnatal Intergrowth-21st charts specifically built on preterm infants were used. Association with major and minor neurodevelopmental impairment at 24-month CA was assessed for each definition. K coefficient and ROC curve were evaluated.Results: Longitudinal “post-loss” definition of EUGR for HC is the one predicting minor neurodevelopmental impairment at the multivariate analysis (OR = 3.94), and it is also associated with a worse General Quotient. The chosen cut-off (Δz-score < −1) is the proper one.Conclusion: HC in-hospital growth could be a more accurate tool than weight to predict neurodevelopmental outcomes and especially minor neurological impairment. Longitudinal “post-loss” definition of EUGR assessed on longitudinal charts for preterm infants could be the most appropriate definition from the methodological, clinical, and prognostic point of view.

Docosahexaenoic acid (DHA) is an essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) and represents the dominant structural fatty acid in the retina and in the brain's gray matter. Due to its active participation in the development of the nervous system, DHA is one of the most studied LCPUFA and is currently considered a critical nutrient during pregnancy and breastfeeding. Increasing evidence in literature suggests that an adequate concentration of DHA is required from the fetal stage through to early life to ensure optimal neurological development. Likewise, many studies in literature demonstrated that an adequate supply of DHA during pregnancy and lactation is essential to promote proper brain development in utero and in early life. Daily supplementation of DHA in newborns has potentially stronger effects compared to maternal supplementation during pregnancy. Supplementation initiated in the second year of life in children born preterm did not result in global cognitive development improvements. Preliminary findings arising from metabolomics has reported that mother's milk and infant formula supplementation of Vitamin D associated with DHA results in a higher antioxidant and protective action, with a possible positive influence on renal function and body fat on preterm infants compared to those receiving only vitamin D. Recent applications of metabolomic studies on newborns may lead to a better understanding of the metabolic process linked to early nutrition and, subsequently, to the development of targeted and personalized nutritional strategies.

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.

Objective: Ensuring cardiorespiratory (CR) stability is essential for a safe discharge. The aim of this study was to assess the impact of a new pre-discharge protocol named CORE on the risk of hospital readmission (RHR). Methods: Preterm infants admitted in our NICU between 2015 and 2018 were randomly assigned to CORE (exposed) or to standard (not-exposed) discharge protocol. CORE included 24 h-clinical observation, followed by 24 h-instrumental CR monitoring only for high-risk infants. RHR 12 months after discharge and length of stay represent the primary and secondary outcomes, respectively. Results: Three hundred and twenty three preterm infants were enrolled. Exposed infants had a lower RHR (log-rank p < 0.05). The difference was especially marked 3 months after discharge (9.09 vs. 21.6%; p = 0.004). The hospital length of stay in exposed and not-exposed infants was 39(26-58) and 43(26-68) days, respectively (p = 0.16). Conclusions: The CORE protocol could help neonatologists to define the best timing for discharge reducing RHR without lengthening hospital stay.

Extrauterine Growth Restriction (EUGR) refers to inadequate growth during hospitalization. Current definitions for EUGR are varied and can be classified as cross-sectional (weight at a given t-time &lt, 10th centile) or longitudinal (weight loss between birth and a given t-time &gt, 1SD). Different t-times are also considered in literature, such as 36 weeks of gestational age (GA) or age at discharge. The aim of this study is to investigate whether EUGR could predict the auxological outcome at 24&ndash, 30 months, and to evaluate the agreement between cross-sectional and longitudinal definitions. In total, 1589 infants with GA &lt, 30 weeks or birthweight &le, 1500 g and without major congenital anomalies were included in this study. Cross-sectional and longitudinal EUGR were calculated at 36 and 40 weeks of GA, at discharge, and at 28 days. The concordance between the two definitions was estimated by Kappa coefficient. At 24&ndash, 30 months, 803 infants were measured again. The agreement between the two definitions of EUGR was low. Both EUGR and not-EUGR groups were at lower centiles for weight, but at higher centiles for head circumference at 24&ndash, 30 months than at birth. Longitudinal EUGR was associated with a poorer growth outcome for weight and height circumference than cross-sectional EUGR. No differences were observed for length. An agreed definition of EUGR is highly desirable in clinical practice to assess medical and nutritional interventions in preterm neonates. Based on the results of this study, we recommend the use of the longitudinal evaluation, that proved to better predict the auxological long-term outcome with respect to the cross-sectional one.

We aimed to evaluate whether electrophysiological auditory thresholds (EATs) before 3 month of age, as assessed by the auditory brainstem responses (ABR) test and the auditory steady state responses (ASSR) test, can predict hearing outcome at 3 years of age among children born with congenital cytomegalovirus (cCMV) infection. Audiological assessment was performed before 3 months of age, and every 6 months thereafter until 3 years of age, in a population of 63 children (126 ears). EATs before 3 months of age and at 3 years of age were compared. No ear with an EAT of ≤30 dBHL (i.e. normal hearing) before 3 months of age showed worsening EATs at 3 years of age. An EAT of ≤30 dBHL obtained by ABR and ASSR tests before 3 months of age is predictive of a normal hearing at 3 years of age in children born with cCMV.

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.

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.

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.

Background The most widespread method for the treatment of donor milk is the Holder pasteurization (HoP). The available literature data show that HoP may cause degradation of some bioactive components. The aim of this study was to determine the effect of HoP on the protein profile of human milk (HM) using a GeLC-MS method, a proteomic approach and a promising technique able to offer a qualitative HM protein profile. Methods HM samples were collected by standardized methods from 20 mothers carrying both preterm and term newborns. A aliquot of each sample was immediately frozen at -80 °C, whilst another one was Holder pasteurized and then frozen. All samples were then analyzed by GeLC-MS. The protein bands of interest were excised from the gel, digested with trypsin and identified by nano-HPLC-MS/MS analysis. Results The protein profile before and after HoP showed qualitative differences only in 6 samples out of 20, while in the remaining 14 no detectable differences were found. The differences interested only colostrums and transitional milk samples and regarded the decrease of the electrophoretic bands corresponding to alpha and beta-casein, tenascin, lactoferrin and immunoglobulin. Conclusions In the majority of samples, HoP did not cause any modification, thereby preserving the biological activity of HM proteins.

Given its unique nutritional and functional advantages, human milk (HM) should be considered as the first choice for the nutrition of all infants, including preterm newborns. Since its protein, mineral and energy contents are not suitable to meet the high needs of very low birth weight (VLBW) infants, HM should be fortified for these components. Fortification of HM is an important nutritional intervention in order to provide appropriate nutritional intake and appropriate growth. The standard fortification strategy has yielded inadequate protein intakes, resulting in slower growth as compared to preterm formulas. Improvement of outcomes depends on new fortification strategies, considering the large variability of HM composition. Individualized fortification, either targeted or adjustable, has been shown to be effective and practical in attaining adequate protein intakes and growth. Most commercially available multi-nutrient fortifiers and protein concentrates are derived from bovine milk (BM), which has a protein composition very different from that of HM. The use of BM proteins has been recently questioned for possible association with intestinal inflammation in VLBW infants. Recently, one HM-based fortifier was shown to be associated with lower necrotizing enterocolitis rates and lower mortality in extremely premature infants, with respect to BM-based products. Other milk sources are currently under evaluation: a randomized, controlled, single-blind clinical trial, coordinated by the Neonatal Unit of the University of Turin in collaboration with the Italian National Research Council of Turin and the University of Cagliari, is being carried out to evaluate the adequacy of fortifiers derived from donkey milk for the nutrition of preterm infants.

There is evidence that mother's own milk is the best nutrient in terms of multiorgan protection and infection prevention. However, when maternal milk is scarce, the solution can be represented by donor milk (DM), which requires specific storage procedures such as Holder Pasteurization (HoP). HoP is not free from side effects since it is widely known that it causes qualitative/quantitative changes in milk composition, particularly in the protein content. Therefore, the aim of this study is to investigate the effects of HoP on Activin A, a neurobiomarker known to play an important role in the development and protection of the central nervous system.In 24 mothers who delivered preterm (n = 12) and term (n = 12) healthy newborns, we conducted a pretest/test study where the milk donors acted as their own controls. Each sample was divided into two parts: the first was frozen at -80°C (Group 1); the second was Holder-pasteurized before freezing at -80°C (Group 2). Activin A was quantified using an ELISA test.Activin A was detected in all samples. There were no significant differences (p 0.05) between the two groups, also when the analysis was stratified for gestational age at delivery and milk maturation degree (p 0.05, for both).The present findings on the absence of any side effects of HoP on the milk concentration of Activin A offer additional support to the efficacy of HoP in DM storage. Our data open up to further investigations on neurobiomarkers' assessment in human milk and their preanalytical stability according to storage procedures.

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.

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.

Mother's own milk is widely recognized as the optimal feeding for term infants, but also provides health benefits that are of vital importance for sick and preterm infants in neonatal intensive care units (NICUs), even though the growth and neurodevelopmental needs of very premature infants are best met by appropriate fortification of human milk (HM). When mother's milk is unavailable or in short supply, donor milk (DM) represents the second best alternative and, although some nutritional elements are inactivated by the pasteurization process, it still has documented advantages compared to formula. Occasionally, the concern that the use of DM might decrease breastfeeding is being raised, but reports exist in literature showing that the use of donor HM in the NICU increases breastfeeding rates at discharge for VLBW infants. The demonstrated benefits of HM highlight the importance of educating health care professionals in breastfeeding support.

Growing clinical evidences indicate the benefits of human milk (HM) for appropriate growth and development of a newborns: the particular composition make it a unique and inimitable nutrient [1]. Mother’s own milk is the first choice for all neonates including preterm infants, when it is unavailable or in short supply, donor milk (DM) is an important alternative. DM should be provided from an established Human Milk Bank (HMB), which follows specific safety guidelines [2]. When HMB is available, significantly less neonatal intensive care unit (NICU) neonates receive formula milk in the first weeks of life. In Italy, data from NICU patients show that exclusive breastfeeding at discharge is achieved for nearly 30% of neonates when banked milk is available during hospitalization and only for 16% of neonates when it is not [3]. DM banking should be promoted, protected, and supported as an extension of national breastfeeding policies, in this regard Italian National Guidelines were published on “Gazzetta Ufficiale della Repubblica Italiana” in 2014 [4]. Nonetheless storage and processing of human milk may reduce some biological components, which may diminish its health benefits but when donor milk is used instead of formula, it is demonstrated a reduction in the incidence of necrotizing enterocolitis and an enhanced feeding tolerance [5]. Pasteurization of the milk is necessary for minimize the risk of disease transmission, inactivating most of the viral and bacterial contaminants. Holder pasteurization (62.5°C for 30 minutes) is the most commonly used method and actually allows a good compromise between microbiological safety and nutritional and biological quality of the milk [2,4]. It results in the loss of the quantity and/or activity of some biologically functional milk components to varying degrees. The optimal pasteurization process should be optimized to maintain microbiological safety while preserving the highest amount and activity of the bioactive milk components. New methods to improve the biological quality and safety of DM are under investigation. High-temperature short-term pasteurization (flash pasteurization, 72°C for 5-15 seconds) and its homemade low-tech variant for developing countries (flash-heat treatment), thermoultrasonic treatment, high-pressure processing are the alternative methods on which present studies are focused. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment on the optimization of DM fortification and on further evaluation of the potential clinical benefits of processed and fortified DM.