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Importance: Respiratory distress syndrome and feeding intolerance are common conditions that are often associated with preterm infants. Showing similar efficacy, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) are the most widespread noninvasive respiratory support (NRS) in neonatal intensive care units, but their effect on feeding intolerance is unknown., Objective: To evaluate the effect of NCPAP vs HHHFNC on high-risk preterm infants with respiratory distress syndrome., Design, Setting, and Participants: This multicenter randomized clinical trial involved infants who were born in 1 of 13 neonatal intensive care units in Italy between November 1, 2018, and June 30, 2021. Preterm infants with a gestational age of 25 to 29 weeks, who were suitable for enteral feeding and who proved to be medically stable on NRS for at least 48 hours were enrolled in the study within the first week of life and randomized to receive either NCPAP or HHHFNC. Statistical analysis was performed according to the intention-to-treat approach., Intervention: NCPAP or HHHFNC., Main Outcomes and Measures: The primary outcome was the time to full enteral feeding (FEF), defined as an enteral intake of 150 mL/kg per day. Secondary outcomes were the median daily increment of enteral feeding, signs of feeding intolerance, effectiveness of the assigned NRS, peripheral oxygen saturation (SpO2)-fraction of inspired oxygen (FIO2) ratio at changes of NRS, and growth., Results: Two-hundred forty-seven infants (median [IQR] gestational age, 28 [27-29] weeks; 130 girls [52.6%]) were randomized to the NCPAP group (n = 122) or the HHHFNC group (n = 125). There were no differences in the primary and secondary nutritional outcomes between the 2 groups. The median time to reach FEF was 14 days (95% CI, 11-15 days) in the NCPAP group and 14 days (95% CI, 12-18 days) in the HHHFNC group, and similar results were observed in the subgroup of infants with less than 28 weeks' gestation. On the first NRS change, higher SpO2-FIO2 ratio (median [IQR], 4.6 [4.1-4.7] vs 3.7 [3.2-4.0]; P < .001) and lower rate of ineffectiveness (1 [4.8%] vs 17 [73.9%]; P < .001) were observed in the NCPAP vs HHHFNC group., Conclusions and Relevance: This randomized clinical trial found that NCPAP and HHHFNC had similar effects on feeding intolerance, despite different working mechanisms. Clinicians may tailor respiratory care by selecting and switching between the 2 NRS techniques on the basis of respiratory effectiveness and patient compliance, without affecting feeding intolerance., Trial Registration: ClinicalTrials.gov Identifier: NCT03548324.

Fortification of human milk (HM) is often necessary to meet the nutritional requirements of preterm infants. This study sought to establish whether HM supplemented with an experimental donkey milk-derived fortifier (DMF) or a commercial bovine milk-derived fortifier (BMF) affected digestion, using an in vitro dynamic system at the preterm stage. Particle size in gastric phase was higher in DMF than in BMF, due to protein aggregates surrounding lipid globules. Before digestion, BMF, with its extensively hydrolysed proteins, had a higher degree of proteolysis (30%) than DMF (11%), which contained intact proteins. After digestion, this difference was reduced concomitantly to a similar net degree of proteolysis (33%). DMF, with a higher proportion of ω3, resulted in a lower ω6/ω3 free PUFA ratio than BMF throughout digestion, although the final degree of lipolysis was similar (54%). In summary, DMF could represent a better source of proteins and lipids for the preterm infant., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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.

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 "Fortilat", 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 "Fortilat" trial at 18 months of age. In the previous trial "Fortilat", 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 ± 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 0-5 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 ± 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.

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 1 H 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.

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 <10th centile) or longitudinal (weight loss between birth and a given t-time >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 24-30 months, and to evaluate the agreement between cross-sectional and longitudinal definitions. In total, 1589 infants with GA <30 weeks or birthweight ≤ 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 24-30 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 24-30 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.

Competing Interests: Competing interests: None declared.

Objectives: 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., Methods: This trial included 156 newborns born at <32 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., Results: 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., Conclusions: These results suggest that DF improve feeding tolerance when compared with standard bovine-derived fortifiers, with a similar auxological outcome.

There is no consensus regarding how the growth of preterm infants should be monitored or what constitutes their ideal pattern of growth, especially after term-corrected age. The concept that the growth of preterm infants should match that of healthy fetuses is not substantiated by data and, in practice, is seldom attained, particularly for very preterm infants. Hence, by hospital discharge, many preterm infants are classified as postnatal growth-restricted. In a recent systematic review, 61 longitudinal reference charts were identified, most with considerable limitations in the quality of gestational age estimation, anthropometric measures, feeding regimens, and how morbidities were described. We suggest that the correct comparator for assessing the growth of preterm infants, especially those who are moderately or late preterm, is a cohort of preterm newborns (not fetuses or term infants) with an uncomplicated intrauterine life and low neonatal and infant morbidity. Such growth monitoring should be comprehensive, as recommended for term infants, and should include assessments of postnatal length, head circumference, weight/length ratio, and, if possible, fat and fat-free mass. Preterm postnatal growth standards meeting these criteria are now available and may be used to assess preterm infants until 64 weeks' postmenstrual age (6 months' corrected age), the time at which they overlap, without the need for any adjustment, with the World Health Organization Child Growth Standards for term newborns. Despite remaining nutritional gaps, 90% of preterm newborns (ie, moderate to late preterm infants) can be monitored by using the International Fetal and Newborn Growth Consortium for the 21st Century Preterm Postnatal Growth Standards from birth until life at home., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background: Charts of size at birth are used to assess the postnatal growth of preterm babies on the assumption that extrauterine growth should mimic that in the uterus., Methods: The INTERGROWTH-21(st) Project assessed fetal, newborn, and postnatal growth in eight geographically defined populations, in which maternal health care and nutritional needs were met. From these populations, the Fetal Growth Longitudinal Study selected low-risk women starting antenatal care before 14 weeks' gestation and monitored fetal growth by ultrasonography. All preterm births from this cohort were eligible for the Preterm Postnatal Follow-up Study, which included standardised anthropometric measurements, feeding practices based on breastfeeding, and data on morbidity, treatments, and development. To construct the preterm postnatal growth standards, we selected all live singletons born between 26 and before 37 weeks' gestation without congenital malformations, fetal growth restriction, or severe postnatal morbidity. We did analyses with second-degree fractional polynomial regression models in a multilevel framework accounting for repeated measures. Fetal and neonatal data were pooled from study sites and stratified by postmenstrual age. For neonates, boys and girls were assessed separately., Findings: From 4607 women enrolled in the study, there were 224 preterm singleton births, of which 201 (90%) were enrolled in the Preterm Postnatal Follow-up Study. Variance component analysis showed that only 0·2% and 4·0% of the total variability in postnatal length and head circumference, respectively, could be attributed to between-site differences, justifying pooling the data from all study sites. Preterm growth patterns differed from those for babies in the INTERGROWTH-21(st) Newborn Size Standards. They overlapped with the WHO Child Growth Standards for term babies by 64 weeks' postmenstrual age., Interpretation: Our data have yielded standards for postnatal growth in preterm infants. These standards should be used for the assessment of preterm infants until 64 weeks' postmenstrual age, after which the WHO Child Growth Standards are appropriate. Size-at-birth charts should not be used to measure postnatal growth of preterm infants., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Villar et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.)

Background: Very low birth weight infants often gain weight poorly and demonstrate growth failure during the initial hospitalization. Although many of the major morbidities experienced by these infants during their initial NICU stays have decreased in recent years, it is unclear whether growth has improved., Methods: We studied 362 833 infants weighing 501 to 1500 g without major birth defects born from 2000 to 2013 and who were hospitalized for 15 to 175 days at 736 North American hospitals in the Vermont Oxford Network. Average growth velocity (GV; g/kg per day) was computed by using a 2-point exponential model on the basis of birth weight and discharge weight. Postnatal growth failure and severe postnatal growth failure were defined as a discharge weight less than the 10th and third percentiles for postmenstrual age, respectively., Results: From 2000 to 2013, average GV increased from 11.8 to 12.9 g/kg per day. Postnatal growth failure decreased from 64.5% to 50.3% and severe postnatal growth failure from 39.8% to 27.5%. The interquartile ranges for the hospitals participating in 2013 were as follows: GV, 12.3 to 13.4 g/kg per day; postnatal growth failure, 41.1% to 61.7%; and severe postnatal growth failure, 19.4% to 36.0%. Adjusted and unadjusted estimates were nearly identical., Conclusions: For infants weighing 501 to 1500 g at birth, average GV increased and the percentage with postnatal growth failure decreased. However, in 2013, half of these infants still demonstrated postnatal growth failure and one-quarter demonstrated severe postnatal growth failure., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: In 2006, WHO published international growth standards for children younger than 5 years, which are now accepted worldwide. In the INTERGROWTH-21(st) Project, our aim was to complement them by developing international standards for fetuses, newborn infants, and the postnatal growth period of preterm infants., Methods: INTERGROWTH-21(st) is a population-based project that assessed fetal growth and newborn size in eight geographically defined urban populations. These groups were selected because most of the health and nutrition needs of mothers were met, adequate antenatal care was provided, and there were no major environmental constraints on growth. As part of the Newborn Cross-Sectional Study (NCSS), a component of INTERGROWTH-21(st) Project, we measured weight, length, and head circumference in all newborn infants, in addition to collecting data prospectively for pregnancy and the perinatal period. To construct the newborn standards, we selected all pregnancies in women meeting (in addition to the underlying population characteristics) strict individual eligibility criteria for a population at low risk of impaired fetal growth (labelled the NCSS prescriptive subpopulation). Women had a reliable ultrasound estimate of gestational age using crown-rump length before 14 weeks of gestation or biparietal diameter if antenatal care started between 14 weeks and 24 weeks or less of gestation. Newborn anthropometric measures were obtained within 12 h of birth by identically trained anthropometric teams using the same equipment at all sites. Fractional polynomials assuming a skewed t distribution were used to estimate the fitted centiles., Findings: We identified 20,486 (35%) eligible women from the 59,137 pregnant women enrolled in NCSS between May 14, 2009, and Aug 2, 2013. We calculated sex-specific observed and smoothed centiles for weight, length, and head circumference for gestational age at birth. The observed and smoothed centiles were almost identical. We present the 3rd, 10th, 50th, 90th, and 97th centile curves according to gestational age and sex., Interpretation: We have developed, for routine clinical practice, international anthropometric standards to assess newborn size that are intended to complement the WHO Child Growth Standards and allow comparisons across multiethnic populations., Funding: Bill & Melinda Gates Foundation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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., (© 2013.)

As for term infants, over the past decades there has been increasing evidence of the benefits of human milk in the feeding of Very Low Birth Weight Infants (VLBWI), influencing not only short-term health outcomes but also long-term neurodevelopmental, metabolic outcomes, and growth. Mother's own milk is the first choice for all neonates including preterm infants, when it is unavailable or in short supply, pasteurized donor breast milk offers a safe alternative and is considered the next best choice. The main aim of this case-control retrospective analysis was to evaluate short term advantages of mother's own milk as a sole diet compared to donor milk as a sole diet, in terms of growth, antiinfectious properties, feeding tolerance, NEC and ROP prevention in a population of VLBWI born in a tertiary center. We did not find significant differences in clinical outcome from mother's own milk compared with pasteurized donor milk. Only a slight and statistically not significant difference in growth could be observed, in favour of maternal milk. We conclude that the maximum effort should always be put in supporting and promoting breastfeeding and donor milk used not only as an alternative to mother's milk but also as a breastfeeding promotion and support strategy.

Preterm infants fed fortified human milk in standard fashion receive less protein than they need due to customary assumptions. Protein is limiting for growth and neurocognitive development,and shortfalls of protein are not acceptable. Adjustable fortification regimen has been proven as an effective way to provide adequate protein intakes and appropriate growth in this group of infants. Italian Association of Human Milk Banks (AIBLUD) has promoted and implemented this Adjustable fortification regimen in neonatal intensive care units (NICUs) with success. This paper presents an update of Adjustable fortification regimen; a new protocol already utilized in several italian NICUs.

Benefits of breastfeeding are widely recognized, during the last decades human milk has been identified as the normative standard for infant feeding and nutrition. Recent evidence focused on specific bioactive and immunomodulatory factors, such as oligosaccharides, lactose, glycosaminoglycans of human milk and the variability of their concentrations during lactation in both term and preterm milk. Human milk should be fortified with proteins, minerals and vitamins to ensure optimal nutrient intake for preterm VLBWI infants. Best fortification strategies as well as the optimal composition of fortifiers are still object of research. Short and long-term clinical, metabolic, immunologic and neurodevelopmental advantages of breastfeeding ndividualizes fortification - particulary adjustable fortification- has proven to be effective when compared to formula are well documented. Moreover several non-experimental studies observed that clinical feeding tolerance is improved and the attainment of full enteral feeding is quicker by a diet of human milk. In addition, benefits of breastfeeding on psychological and relational aspects have to be considered. Mother’s own milk remains the first choice for all neonates, when it is not available or not sufficient despite significant lactation support, donor milk represents the second best alternative and although some nutritional elements are inactivated by the pasteurization process, it still has documented advantages compared to formula.

Preterm infants' survival has greatly increased in the last few decades thanks to the improvement in obstetrical and neonatal care. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth, specifically in relation to the charts used. At present, the charts available in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. Recently, an international project has recently started aiming to create prescriptive standard for the evaluation of postnatal growth of preterm infants (INTERGROWTH-21st). Alternatively, at present, while specific charts for evaluating preterm infant postnatal growth are lacking, the best compromise is likely to be as follows: from birth to term neonatal anthropometric charts; International longitudinal charts WHO 2006 or CDC 2002 from term to childhood.

In a NICU early enteral feeding is usually possible only when the newborn clinical conditions permit it. Because of the frequent need of umbilical/central catheters, they usually start with parenteral feeding and/or with minimal enteral feeding (trophic feeding). This kind of management is even more frequent in VLBWIs, in which the risk of NEC is very high. In this work we describe a model of early enteral exclusive feeding (EEEF) based on the use of banking human milk followed by mother milk. In the Centre of Neonatology of Trento, as in other Centers, the newborns weighing less than 750g or with a GE< 27 weeks, are treated with parenteral nutrition and minimal enteral feeding. The newborn weighing 750-1249g and with GE > 26 weeks define a group in which we find critical neonates, who can not be treated with enteral feeding, and neonates whose clinical conditions permit EEEF. In particular, in a period of 16 years (1994-2009) in Trento, 308 newborns weighing 750-1249 g and GE > than 26 weeks were admitted. The 90,9 % has been treated with prenatal steroids, the 91,9 % was inborn, the 96,1% survived. In the 59,1 % of the cases (175) we gave EEEF. We could continue with a complete EEEF in the 40,2 % of the total (119 cases). The characteristics of these neonates and our centre management, based mainly on early use of banking human milk and mother milk, are detailed described.

Postnatal growth restriction and failure to thrive still remain a major problem in Extremely Low Birth Weight (ELBW) infants . The goal for the nutritional care of these infants is to achieve rate of growth similar to those of the fetus in utero at the equivalent gestational age. Human milk fortified remains the best food for all these preterms. Two groups of preterm of weight 580-1250 g and gestational age 23-32 wk, were fed with different protein intake in the human/maternal milk fortified ( 3,5 g Kg-1 per day and 4,8 g Kg-1 per day in the control and intervention group respectively).The feeding tolerance, intrahospital growth, neurological outcome and anthropometric data until 12 months of corrected age, were evaluated. The protein supplemented group (PSG) showed an intrahospital highter growth rate ( mostly in head circumference, p 0,02, and length growth, p 0,04) only in the preterms with 580-980 g and 23-30 wk. In the same preterms, Griffith Development Mental Score at 3 and 12 months corrected age showed higher score than in the control group in the Performance (p 0,04) and Hearing/Language (p 0,03) items. The auxological evaluation in the postdischarge period showed in the PSG group mean z-score values for length higher than those in the control group at 9 (p 0,04) months of corrected age.

The past two decades have seen a progressive improvement in the survival rates of preterm infants, especially in neonates <30 weeks of gestational age. These neonates constitute the large majority of the population in neonatal intensive care units. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth, specifically in relation to the charts used. At present the available charts in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. An international multicentric project has recently started a study aiming at building a prescriptive standard for the evaluation of postnatal growth of preterm infants and it will be available in the next years providing a population that is conceptually as close as possible to the prescriptive approach used for the construction of the WHO infant and child growth standards. At present, while an international longitudinal standard for evaluating preterm infant postnatal growth is lacking, in Italy the best compromise in clinical practice is likely to be as follows: new Italian INeS (Italian Neonatal Study) charts up to term; International longitudinal charts WHO 2006 or CDC 2002 from term to two years; finally the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) 2006 growth charts could be suitable for monitoring the growth of these infants from two years up to 20 years of age.

Monitoring and interpreting the growth of preterm infants is a major clinical task for neonatologists. The effectiveness of this process depends upon the robustness of the standard selected. Concerns have been raised regarding the nature of the charts currently being used, as well as their appropriateness for present-day neonatal care. To overcome these problems, there is a need for new prescriptive standards based on a population of preterm infants without evidence of impaired fetal growth and born to low-risk women followed up since early pregnancy for precise gestational age dating. Preterm infants contributing to the new standards should be free of congenital malformations and major clinical conditions associated with impaired postnatal growth. These infants should receive standardised, evidence-based clinical care and should follow current feeding recommendations based on exclusive/predominant breastfeeding. This strategy should provide a population that is conceptually as close as possible to the prescriptive approach used for the construction of the WHO infant and child growth standards. New international standards constructed in this way should contribute to the evidence-based care of these preterm infants.

Preterm Infants' survival has greatly increased in the last few decades thanks to the improvement in obstetrical and neonatal care. These neonates constitute the large majority of the population in neonatal intensive care units. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth,specifically in relation to the charts used. At present the available charts in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. An international multicentric project has recently started a study aiming at building a prescriptive standard for the evaluation of postnatal growth of preterm infants and it will be available in the next years. At present, while an international longitudinal standard for evaluating preterm infant postnatal growth is lacking, in Italy the best compromise in clinical practice is likely to be as follows: new Italian INeS (Italian Neonatal Study) charts up to term; International longitudinal charts WHO 2006 or CDC 2002 from term to two years; finally, the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) 2006 growth charts could be suitable for monitoring the growth of these infants from two years up to 20 years of age.

Milk fat globule membrane (MFGM) proteins constitute a milk fraction currently of great interest, as they appear to significantly contribute to milk protective role. We investigated these proteins in human preterm colostrum and milk. For the former we found a peculiar 2-DE pattern, with a spot concentration at low molecular weight, which mass spectrometry analysis showed to be fragments belonging to some MFGM proteins with a well-known biological and especially immunological role: lactadherin, membrane-associated lactoferrin, butyrophilin, clusterin and heavy-chain immunoglobulin. Since we were able to rule out protease activity after specimen collection, we hypothesize the localization of the proteolytic enzymes in the alveolar cell membranes of the mammary gland. This mechanism is probably under hormonal control and the unexpected advent of preterm delivery would not allow hormonal conditions typical of lactation to occur immediately, causing a delay in enzymatic inhibition. This hypothesis is supported by some of our results, picturing a peculiar transient phenomenon of adaptation of the mammary-gland-membrane proteins after preterm delivery. Further studies will be required to verify whether the presence of protein fragments exerts a specific biological and immuno-defensive role in preterm infants, thus adding evidence to the outstanding biological role and benefits of mother's own milk in feeding preterm infants.

Aims: To evaluate the metabolic pattern of a group of pre-school small- (SGA) and appropriate-for-gestational age (AGA) pre-term very-low-birthweight (VLBW) (<1500 gr) Italian children and retrospectively verify if the growth rate in the first years of life is associated to the laboratory and anthropometric characteristics of these children., Methods: 58 (16 SGA, 42 AGA) VLBW children, without major congenital malformations/conditions were enrolled; their anthropometric, clinical and (in 34 of them) laboratory characteristics were evaluated at pre-school age (> 2<6 years of corrected age)., Results: Clinical, anthropometric and laboratory characteristics at pre-school age were similar in SGA and AGA. Sixty-nine percent of SGA and 51% of AGA children showed a significant weight centile crossing (CC) at 24 months. Fasting serum glucose, insulin and insulin resistance (evaluated by the Homeostasis Model Assessment -HOMA-IR-) were higher in AGA and SGA with CC. The increment in weight standard deviation scores from birth-to-24 months was significantly associated with pre-school BMI SDS, waist, fasting insulin, and HOMA-IR values, both in unadjusted and adjusted models. In a multiple regression model, after multiple adjustments, this increment is the only significant predictor of pre-school insulin (B = 0.19; 95%CI 0.07-0.31; P = 0.006) and HOMA-IR levels (B = 0.20; 95%CI 0.08-0.32; P = 0.004) both in SGA and AGA children., Conclusions: The adverse metabolic pattern of pre-school VLBW children seems related to post-natal events (rapid weight growth) independently by their being small- or appropriate-for gestational age.