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High Temperature-Short Time (HTST) pasteurization was proposed as an alternative to Holder pasteurization (HOP) to increase the retention of specific human milk (HM) bioactive proteins. The present study explored whether HTST and HOP differently affect peptide release during simulated preterm infant gastrointestinal digestion. Raw (RHM), HOP- and HTST- pasteurized HM were digested using an in vitro dynamic system, and the identified peptides were analyzed by mass spectrometry and multivariate statistics. Before digestion, 158 peptides were identified in either RHM, HTST- or HOP- HM, mostly (84.4%) originating from ?-casein (CASB). During gastric digestion, HOP-HM presented a greater number and more abundant specific CASB peptides. A delayed release of peptides was observed in RHM during the intestinal phase, with respect to both pasteurized HM. Although limited to gastric digestion, the HM peptidomic profile differed according to the pasteurization type, and the pattern of the HTST peptides showed a greater similarity with RHM.

The late preterm (LP) rate in Western countries is 3–6% of all births, accounting for about two-thirds of the entire preterm population. However, all LP babies are not the same. To identify pregnancies at risk for adverse outcomes in the LP period, we investigated how gestational age (GA) at delivery, delivery indication and prenatal risk factors may affect neonatal outcomes. Prospective cohort study among singleton infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Multivariate logistic regression models were used to, respectively, investigate the effects of GA at delivery, circumstances at parturition and prenatal risk factors, on study outcomes after controlling for confounding variable. Among 1867 births, 302, 504, and 1061 infants were born at 34, 35, and 36 weeks, respectively. There were no neonatal deaths. An increased risk of composite neonatal outcome was observed among 34 and 35 weeks deliveries compared with 36 weeks, and among indicated deliveries compared with spontaneous. When studying prenatal risk factors, neonatal morbidity was associated with pre gestational diabetes, preterm premature rupture of membranes (pPROM), maternal obesity, bleeding and polyhydramnios; instead, preeclampsia had a protective effect. LP with indicated deliveries at 34 or 35 weeks, or with specific prenatal risk factors have worse neonatal outcome when compared to 36. Such differences should be considered when counseling patients and planning interventions such as timing of delivery in LP period.

Background Respiratory distress syndrome (RDS) and feeding intolerance are common conditions in preterm infants and among the major causes of neonatal mortality and morbidity. For many years, preterm infants with RDS have been treated with mechanical ventilation, increasing risks of acute lung injury and bronchopulmonary dysplasia. In recent years non-invasive ventilation techniques have been developed. Showing similar efficacy and risk of bronchopulmonary dysplasia, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) have become the most widespread techniques in neonatal intensive care units. However, their impact on nutrition, particularly on feeding tolerance and risk of complications, is still unknown in preterm infants. The aim of the study is to evaluate the impact of NCPAP vs HHHFNC on enteral feeding and to identify the most suitable technique for preterm infants with RDS. Methods A multicenter randomized single-blind controlled trial was designed. All preterm infants with a gestational age of 25–29 weeks treated with NCPAP or HHHFNC for RDS and demonstrating stability for at least 48 h along with the compliance with inclusion criteria (age less than 7 days, need for non-invasive respiratory support, suitability to start enteral feeding) will be enrolled in the study and randomized to the NCPAP or HHHFNC arm. All patients will be monitored until discharge, and data will be analyzed according to an intention-to-treat model. The primary outcome is the time to reach full enteral feeding, while parameters of respiratory support, feeding tolerance, and overall health status will be evaluated as secondary outcomes. The sample size was calculated at 141 patients per arm. Discussion The identification of the most suitable technique (NCPAP vs HHHFNC) for preterm infants with feeding intolerance could reduce gastrointestinal complications, improve growth, and reduce hospital length of stay, thus improving clinical outcomes and reducing health costs. The evaluation of the timing of oral feeding could be useful in understanding the influence that these techniques could have on the development of sucking-swallow coordination. Moreover, the evaluation of the response to NCPAP and HHHFNC could clarify their efficacy as a treatment for RDS in extremely preterm infants. Trial registration ClinicalTrials.gov, NCT03548324. Registered on 7 June 2018. Electronic supplementary material The online version of this article (10.1186/s13063-018-3119-0) contains supplementary material, which is available to authorized users.

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 121 kb)

baCkgrounD: Very preterm newborns (gestational age lower than 32 weeks) and Very low birthweight (VlbW) infants (birthweight lower than 1500 grams) currently represent the majority of patients cared in neonatal intensive Care units (niCu). the increase of the survival rate for these newborns, due to improvements in perinatal care, has opened new perspectives regarding their outcome and has a significant impact on their health status in adulthood. in these groups of infants, nutrition represents a fundamental factor not only for neonatal survival and short-term outcome, but also for long-term consequences and quality of life. the main issue is to ensure an adequate qualitative and quantitative nutrition, particularly in terms of protein intake, which is the main cause of post-natal growth deficit [1]. Human milk is the recommended food for all neonates including preterm infants [2]. breast milk alone, however, does not meet the recommended nutritional needs in preterm infants [3]. the most common strategy is to cope with potential nutrient deficits by supplementing breast milk with additional nutrients (mainly proteins and minerals) to satisfy the special nutritional requirements of these infants[4]. at present commercially available fortifiers are based on bovine milk (bM), whose protein intake has raised concerns because of its association with allergies [5] and a possible role as a trigger of intestinal inflammation in preterm neonates [6]. in previous studies we observed that donkey milk (DM) was well tolerated in a group of highly problematic cow's milk allergic children [7]. our hypothesis is that feeding preterm infants with HM supplemented with fortifiers derived from DM will improve the feeding tolerance. aiM. the purpose of the present randomized clinical trial is to compare the use of DM-derived fortifiers with commercial bMbased fortifiers in infants with birthweight =80ml/kg/day reached within the first 4 weeks of life. the neonates affected by severe gastrointestinal pathologies, chromosomal abnormalities or major malformations, metabolic diseases, intravascular disseminated coagulopathy, shock, patent ductus arteriosus requiring medical care or surgery at time of randomization, and severe renal failure were excluded. before the beginning of this study, approximately 45% VlbWi or preterm infants admitted to our niCu had at least one episode of feeding intolerance. a 25% reduction in the frequency of the primary endpoint was regarded as the minimum clinically important difference (MCiD): 62 infants per arm (planned study) had to be recruited to ensure an 80% study power, if the risk of type i error is set to the usual level of 5%. Since the occurrence of primary endpoint in our study population resulted to be much lower than that assumed in the protocol, and no adverse effect was observed, when the planned study size was achieved, it was decided to continue the enrollment until the end of the stock of fortilat (extended study). infants were randomized 1:1 by a software-generated list in two arms: bf-arm (bovine fortifier) and Df-arm (Donkey fortifier). observation period was defined as 21 days since the beginning of fortification. in bf-arm, the human milk was fortified with commercial multi-component fortifier (fM85 nestlè) and protein concentrate (protifar nutricia), derived from bovine milk, while in Df-arm with multi-component fortifier and protein concentrate derived from donkey milk (fortilat), produced by an ultrafiltrationprocess of pasteurized donkey milk in a pilot stainless steel. advancing of enteral feeds was strictly regulated according to the feeding protocol adopted in our niCu, based on the evaluation of signs of feeding intolerance. the primary endpoint was the occurrence of at least one episode of feeding intolerance, defined as interruption of enteral feeding for at least 8 consecutive hours during the observation period. We also evaluated the total number of feeding intolerance episodes and the number of feeding interruption episodes of any duration. Statistical analysis. in the intention-to-treat population (itt, all randomized infants) failure included the occurrence of at least one episode of feeding intolerance, neC, death, and transfered before 21 days of observation. the difference in the occurrence of failure (primary endpoint) between the two arms of the trials was tested with fisher's exact test. reSultS. a total of 124 neonates were enrolled in planned study (bf-arm n= 62; Df-arm n=62). further 32 infants were enrolled in extended study (bf-arm n= 79, Df-arm n=77). the primary risk of failure in the planned sample has resulted lower in Df-arm than in bf-arm with a relative risk reduction (rrr) [Ci(95%)] of 0.40 [-0.27; +0.72]. the trend of these results was similar in the extended sample: 0.46 [ 0.09; +0.73]. the mean [iC(95%)] of the total episodes of feeding intolerance and the mean [iC(95%)] of enteral feeding interruptions of any duration was lower in Df-arm (0.11 [0.01; 0.21] and 0.27 [0.12; 0.42] respectively) than in bf-arm (0.20 [0.07; 0.34] and 0.39 [0.20; 0.57] respectively). DiSCuSSion. our first results about donkey milk based fortifiers are promising. Compared to the bovine fortifiers, the donkey milk based fortifier seems to have a better feeding tolerance even if these results are not significant. When we extended the study including more patients (extended sample), we observed a further slight improvement in feeding tolerance in favor of the Df-arm. We can therefore hypothesize that increasing the sample size we would observe a significant better feeding tolerance in Df-arm. to confirm our data it will be useful to perform a multicenter study in order to increase the sample size. it will be interesting to analyze metabolic, auxological and neurodevelopmental outcomes in order to determine if the use of donkey milk fortifiers will have also long-term benefits.

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, compared 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.

The outcome of bloodstream infections (BSIs) is strongly related to microbiological diagnosis. Several factors may reduce blood culture (BC) diagnostic yield in pediatric BSIs, making the application of molecular methods quite promising.Multiplex real-time polymerase chain reaction (PCR) tests (the LightCycler Septifast Test MGRADE by Roche Diagnostics--LC-SF) performed in the tertiary centre of Regina Margherita Children's Hospital (Turin, Italy) over a 3-year period were retrospectively evaluated. Results of the LC-SF test were compared with those of BC (Automated Bact/Alert 3D, Biomerieux) collected at a close time point.545 LC-SF tests were collected from 289 patients (183 males, median age 6.8 years, interquartile range (IQR) = 2.7-13.1); 163 had congenital or acquired immunodeficiency. In 515 cases (94.5%) the LC-SF test was performed with ongoing empirical antimicrobial therapy. Etiological definition was achieved in 111 BSI cases (20.4%). Both LC-SF and BC identified the responsible pathogen in 39 episodes. The LC-SF test alone gave a positive result in 29 septic episodes; BC alone permitted the etiological diagnosis in 43 episodes, but isolates were not included in the LC-SF master list in 10 cases. A 26% increase in bacterial identification chances due to the LC-SF test was documented. Cohen's kappa test indicated a moderate strength of agreement (0.49) between LC-SF tests and BCs closely collected.BC remains the gold standard for the etiological diagnosis of BSIs, but PCR methods proved to be a valuable adjunctive diagnostic tool in pediatric BSIs, especially in children receiving empirical chemotherapy.

Mother’s own milk (MOM) is the first choice in preterm infant feeding, and when it is not available or is insufficient, donor human milk (DHM) is recommended. It has been shown that feeding preterm infants with human milk is less related to major morbidities, enhances feeding tolerance and prevents metabolic syndrome in childhood. As The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) states, specific guidelines for Human Milk Banks (HMB) are needed to guarantee the best possible compromise between microbiological safety and nutritional/biological quality of human milk (HM). Currently, Holder pasteurization (HoP: pasteurization process at 62.5-63°C for 30 minutes) is recommended by all international guidelines: this method inactivates bacterial and viral pathogens but it also affects some nutritional and biological properties of human milk. New methods to ameliorate the biological quality and safety of DHM are under investigation in the last years. High Pressure Processing (HPP) is a non- thermal process used in food industries: this technology inactivates pathogenic microorganisms by applying hydrostatic high pressure, however further researches are required before applying this technology in milk banking. Ultraviolet-C irradiation (UV-C) is another non-thermal method capable of reducing vegetative bacteria in human milk and it also seems to preserve higher levels of immunological proteins than HoP. High-temperature short-time pasteurization (HTST: flash pasteurization, 72°C for 5-15 seconds) currently is available only at industrial level, but it could represent an alternative to HoP seeming to maintain the protein profile and some of the key active components of DHM. Further researches are needed to define the optimal treatment of DHM. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy) · October 26th-31st, 2015 · From the womb to the adult Guest Editors: Vassilios Fanos (Cagliari, Italy), Michele Mussap (Genoa, Italy), Antonio Del Vecchio (Bari, Italy), Bo Sun (Shanghai, China), Dorret I. Boomsma (Amsterdam, the Netherlands), Gavino Faa (Cagliari, Italy), Antonio Giordano (Philadelphia, USA)

Francesca Giuliani,1 Ilaria Rovelli,1 Chiara Peila,1 Stefania Alfonsina Liguori,2 Enrico Bertino,1 Alessandra Coscia1 1SCDU Neonatologia, Dipartimento di Scienze Pediatriche e dell'Adolescenza, Università degli Studi di Torino, Torino, Italy; 2SC Neonatologia, Ospedale Maria Vittoria, Torino, Italy Abstract: Mother's own milk is widely recognized as the optimal feeding for term infants, but increasing evidence exists of its benefits also for sick and preterm infants in neonatal intensive care units. However, the nutritional needs for appropriate growth and neurodevelopmental outcomes of such a particular population of infants should be attentively evaluated, considering also the indication to an appropriate fortification of human milk. The target is to achieve growth potential for preterm newborns while ensuring good metabolic outcomes and normal neurological development. When mother's milk is unavailable or in short supply, donor human milk (DHM) represents the second best choice and, although somewhat modified by the Holder pasteurization process, it preserves many benefits when compared to formula, as documented by more and more reports, randomized controlled trials, and meta-analyses published in the past few years. Evidence exists of the protection exerted by DHM from necrotizing enterocolitis, while further studies are required to look at possible beneficial effects regarding infections, bronchopulmonary dysplasia, long-term cardiovascular risk factors, feeding tolerance, neurological outcome, and allergy. Finally, the concern that the use of DHM might decrease preterm infant breastfeeding is being raised. Conversely, publications exist showing that the use of DHM in the neonatal unit increases breastfeeding rates at discharge for infants of very low birth weight. Keywords: human milk, preterm infant feeding, milk bank, breast milk, mother's own milk, pasteurized human milk, fortification

Breastfeeding and human milk are the normative standards for feeding and nutrition of both term and pre-term infants. Fresh mother’s own milk is recognized as the optimal choice for feeding all newborns, including preterm and very low birth weight infants. Evidence documents short and long-term metabolic, immunologic and neurodevelopmental advantages of breastfeeding when compared to formula. Moreover, benefits of breastfeeding on psychological and relational aspects have to be considered. Currently, human milk supplementation is usually performed to meet the specific nutritional requirements of preterm infants. When mother’s milk is unavailable or in short supply, donor milk represents the best alternative, although some nutritional elements are inactivated by the necessary pasteurization process. Aim of this review is to briefly summarize the main biological and nutritional factors that contribute to the beneficial effects of human milk feeding for preterm infants.

Background Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Results Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p p p p p p p p p p Conclusion Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants’ prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications.

Background: The aim of this systematic review is to analyze the available literature on the introduction of allergenic foods and gluten among preterm infants. Methods: A systematic review of published studies concerning the introduction of gluten and allergenic foods in preterm infants was performed on PubMed and on the Cochrane Library. Results: Of the 174 PubMed results, 15 papers were considered suitable for the review. A total of 83 records were identified through the Cochrane Library search; eight papers were included in the review. Additional papers were identified from the reference lists of included studies. A secondary search was conducted on the same databases to find recommendations and advice regarding healthy full-term infants that could be translated to preterm infants. Therefore, 59 additional papers were included in the review. Conclusions: Current guidelines for the introduction of solid food cannot be directly transposed to preterm infants. Further research is needed to provide evidence-based guidelines regarding weaning in preterm infants. To date, we can suggest that in preterm infants allergenic foods and gluten may be introduced when complementary feeding is started, any time after 4 months of corrected age, avoiding delayed introduction and irrespective of infants’ relative risk of developing allergy. Avoiding large amounts of gluten during the first few weeks after gluten introduction and during infancy is advised, despite limited evidence to support this recommendation.