Impact of macronutrients intake on glycemic homeostasis of preterm infants: evidence from continuous glucose monitoring.

Nutritional intake could influence the blood glucose profile during early life of preterm infants. We investigated the impact of macronutrient intake on glycemic homeostasis using continuous glucose monitoring (CGM). We analyzed macronutrient intake in infants born ≤ 32 weeks gestational age (GA) and/or with birth weight ≤ 1500 g. CGM was started within 48 h of birth and maintained for 5 days. Mild and severe hypoglycemia were defined as sensor glucose (SG) < 72 mg/dL and <47 mg/dL, respectively, while mild and severe hyperglycemia were SG > 144 mg/dL and >180 mg/dL. Data from 30 participants were included (age 29.9 weeks (29.1; 31.2), birthweight 1230.5 g (1040.0; 1458.6)). A reduced time in mild hypoglycemia was associated to higher amino acids intake (p = 0.011) while increased exposure to hyperglycemia was observed in the presence of higher lipids intake (p = 0.031). The birthweight was the strongest predictor of neonatal glucose profile with an inverse relationship between the time spent in hyperglycemia and birthweight (p = 0.007).  Conclusions: Macronutrient intakes influence neonatal glucose profile as described by continuous glucose monitoring. CGM might contribute to adjust nutritional intakes in preterm infants. What is Known: • Parenteral nutrition may affect glucose profile during the first days of life of preterm infants. What is New: • Continuous glucose monitoring describes the relationship between daily parenteral nutrient intakes and time spent in hypo and hyperglycemic ranges.

Complementary feeding in infants born preterm: Aspects needing improvement.

Objective: The aim of our study was to collect data on complementary feeding (CF) in preterm infants (PIs). Methods: We enrolled PI ≤ 34 weeks of gestational age discharged from the neonatal intensive care unit (NICU) of the University Hospital of Padova. At 12 months of corrected age (CA), CF was investigated with questionnaires to the parents and a 24-h dietary recall. In a subgroup of newborns, we also evaluated bone status at a CA of 12 months using quantitative ultrasound. Results: We studied 167 ex PI at 1 year of CA. CF was introduced in 67.1% of them between 5 and 8 months of chronological age, with fruit as the first food (81%, n = 136). Sweet drinks were consumed by 17.4% of our sample, and salt was added in 33.5% of cases. PIs, at 1 year CA, introduced extra energy compared to the theoretical requirement (121 ± 31 kcal/kg/day) and higher protein intake than recommended (39 ± 11 g/day), while the intake of both total lipids and carbohydrates was slightly lower. Vitamins and minerals were adequate, except vitamin D. Regarding bone status, we found a correlation between vitamin D intakes from the diet and bone parameters (metacarpus-bone transmission time: r = 0.36, p = 0.01) at 1 year of CA. Conclusions: Our population of PIs started CF in agreement with current suggestions though with a notable heterogeneity and with some mistakes. Vitamin D intake was correlated with bone status at 1 year of CA.

Bone Status and Early Nutrition in Preterm Newborns with and without Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) together with preterm birth could be harmful to bone health. The aim of the study was to examine bone status in IUGR versus non-IUGR preterms and to analyze the nutritional management best correlated with its improvement. Newborns < 34 weeks of gestational age (wGA), 75 IUGR and 75 non-IUGR, admitted to the Neonatal Intensive Care Unit of the University Hospital of Padova were enrolled and monitored from birth until 36 wGA through anthropometry (weight, length, head circumference, lower limb length (LLL)), biochemistry, bone quantitative ultrasound assessment of bone status (metacarpus bone transmission time, mc-BTT, us) and nutritional intakes monitoring during parenteral nutrition. IUGR compared to non-IUGR showed lower mean mc-BTT (0.45 vs. 0.51, p = 0.0005) and plasmatic phosphate (1.45 vs. 1.79, p < 0.001) at birth. Mc-BTT at 36 wGA, though equal between groups, correlated in IUGR newborns with basal phosphate, mean total energy of the first week and month (positively) and days to reach full enteral feeding (negatively). Lower i.v. vitamin D intake, LLL and prolonged total parenteral nutrition predicted worse mc-BTT at 36 wGA in the enrolled infants. These results suggest that preterms and in particular IUGR newborns need special nutritional care to promote bone development.

Prematurity and BPD: what general pediatricians should know.

More and more very low birth weight (VLBW) infants around the world survive nowadays, with consequently larger numbers of children developing prematurity-related morbidities, especially bronchopulmonary dysplasia (BPD). BPD is a multifactorial disease and its rising incidence in recent years means that general pediatricians are much more likely to encounter a child born extremely preterm, possibly with BPD, in their clinical practice. Short- and long-term sequelae in VLBW patients may affect not only pulmonary function (principally characterized by an obstructive pattern), but also other aspect including the neurological (neurodevelopmental and neuropsychiatric disorders), the sensorial (earing and visual impairment), the cardiological (systemic and pulmonary hypertension, reduced exercise tolerance and ischemic heart disease in adult age), nutritional (feeding difficulties and nutritional deficits), and auxological (extrauterine growth restriction). For the most premature infants at least, a multidisciplinary follow-up is warranted after discharge from the neonatal intensive care unit in order to optimize their respiratory and neurocognitive potential, and prevent respiratory infections, nutritional deficiencies or cardiovascular impairments.  Conclusion: The aim of this review is to summarize the main characteristics of preterm and BPD infants, providing the general pediatrician with practical information regarding these patients' multidisciplinary complex follow-up. We explore the current evidence on respiratory outcomes and their management that actually does not have a definitive available option. We also discuss the available investigations, treatments, and strategies for prevention and prophylaxis to improve the non-respiratory outcomes and the quality of life for these children and their families, a critical aspect not always considered. This comprehensive approach, added to the increased needs of a VLBW subjects, is obviously related to very high health-related costs that should be beared in mind. What is Known: • Every day, a general pediatrician is more likely to encounter a former very low birth weight infant. • Very low birth weight and prematurity are frequently related not only with worse respiratory outcomes, but also with neurological, sensorial, cardiovascular, renal, and nutritional issues. What is New: • This review provides to the general pediatrician a comprehensive approach for the follow-up of former premature very low birth weight children, with information to improve the quality of life of this special population.

Prenatal environment and developmental trajectories: the intrauterine growth restriction.

The prenatal environment is of fundamental importance for the fetus, as the fetus is particularly susceptible to environmental influences while in utero, and several prenatal adversities may constitute a risk factor for fetal growth and child development. Intrauterine growth restriction (IUGR) refers to a pregnancy complication involving the inadequate growth of the fetus in utero, with potential programming consequences on the children's brain-behavior development. In this narrative review we will discuss the most recent literature about IUGR children, including their development and their relationship with the prenatal and postnatal environment. In particular, as an attempt to an adaptive response to intrauterine changes, the brain development of IUGR fetuses follows abnormal developmental pathways, which likely has cascade effects on the future neurodevelopmental outcomes of the children. Cognitive and motor functions are in fact impaired, as well as IUGR children present, across studies, poor socio-emotional abilities and a greater risk for internalizing and externalizing behavior problems. The current work also highlights how the postnatal environment, and in particular parental care, has an important role in IUGR development, acting as a protective factor, or otherwise increasing their constitutional vulnerabilities. Overall, this narrative review has important implications for clinical practice, suggesting the need for long-term follow-up care with IUGR children and strategies supporting parent-child interactions as well.

Metabolomic profiling of intrauterine growth-restricted preterm infants: a matched case-control study.

BACKGROUND: The biochemical variations occurring in intrauterine growth restriction (IUGR), when a fetus is unable to achieve its genetically determined potential, are not fully understood. The aim of this study is to compare the urinary metabolomic profile between IUGR and non-IUGR very preterm infants to investigate the biochemical adaptations of neonates affected by early-onset-restricted intrauterine growth. METHODS: Neonates born <32 weeks of gestation admitted to neonatal intensive care unit (NICU) were enrolled in this prospective matched case-control study. IUGR was diagnosed by an obstetric ultra-sonographer and all relevant clinical data during NICU stay were captured. For each subject, a urine sample was collected within 48 h of life and underwent untargeted metabolomic analysis using mass spectrometry ultra-performance liquid chromatography. Data were analyzed using multivariate and univariate statistical analyses. RESULTS: Among 83 enrolled infants, 15 IUGR neonates were matched with 19 non-IUGR controls. Untargeted metabolomic revealed evident clustering of IUGR neonates versus controls showing derangements of pathways related to tryptophan and histidine metabolism and aminoacyl-tRNA and steroid hormones biosynthesis. CONCLUSIONS: Neonates with IUGR showed a distinctive urinary metabolic profile at birth. Although results are preliminary, metabolomics is proving to be a promising tool to explore biochemical pathways involved in this disease. IMPACT: Very preterm infants with intrauterine growth restriction (IUGR) have a distinctive urinary metabolic profile at birth. Metabolism of glucocorticoids, sexual hormones biosynthesis, tryptophan-kynurenine, and methionine-cysteine pathways seem to operate differently in this sub-group of neonates. This is the first metabolomic study investigating adaptations exclusively in extremely and very preterm infants affected by early-onset IUGR. New knowledge on metabolic derangements in IUGR may pave the ways to further, more tailored research from a perspective of personalized medicine.

Glucose variability increases during minimally invasive procedures in very preterm infants.

The objective of this study is to assess the effect of neonatal procedures on glucose variability in very preterm infants. Preterm infants (≤ 32 weeks gestation and/or birthweight ≤ 1500 g) were started on continuous glucose monitoring (CGM) on day 2 of birth and monitored for 5 days. Minimally invasive (heel stick, venipunctures) and non-invasive (nappy change, parental presence) procedures were recorded. CGM data were analyzed 30 min before and after each procedure. The primary outcome was the coefficient of glucose variation (CV = SD/mean) before and after the procedure; SD and median glucose were also evaluated. We analyzed 496 procedures in 22 neonates (GA 30.5 weeks [29-31]; birthweight 1300 g [950-1476]). Median glucose did not change before and after each procedure, while CV and SD increased after heel prick (p = 0.017 and 0.030), venipuncture (p = 0.010 and 0.030), and nappy change (p < 0.001 and < 0.001), in the absence of a difference during parental presence. CONCLUSIONS: Non-invasive and minimally invasive procedures increase glucose variability in the absence of changes of mean glucose. WHAT IS KNOWN: • Minimally invasive procedures - including nappy change - may increase neonatal stress in preterm infants. WHAT IS NEW: • Continuous glucose monitoring provides a quantitative measure of neonatal stress during neonatal care procedures demonstrating an increase of glucose variability.

Successful Control of an Outbreak by Phenotypically Identified Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae in a Neonatal Intensive Care Unit.

BACKGROUND: Premature newborns represent a vulnerable population, at high risk of acquiring nosocomial infections during neonatal intensive care unit (NICU) admission. Multidrug-resistant organisms represent the greatest concern due to their intrinsic virulence and the limited therapeutic options. Resistant Enterobacterales are a growing threat for critically ill neonates, with increasing numbers of NICU outbreaks caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales being described. This study reports the early detection and successful control of an outbreak caused by ESBL-producing Klebsiella pneumoniae (ESBL-KP) in an Italian NICU in February 2021. RESULTS: A total of 13 newborns tested positive for ESBL-KP between 2-9 February 2021, of whom four (31%) had a bloodstream infection. Two were critically ill, extremely premature newborns who died because of multiple comorbidities, and two were cured after treatment with meropenem. All other patients survived and were either discharged home or moved to other hospitals/wards in good clinical condition. ESBL-KP ST45 was found in all isolates by multilocus sequence typing (MLST) analysis. An outbreak control plan was set, including surveillance cultures for all neonates, NICU environments, and medical devices, along with the extended use of contact precautions and cohorting. In addition, the infection control plan was carried out through reinforcement and enhancement measures to guarantee maximal compliance. The outbreak was successfully controlled in seven days, given that no further cases were identified after 9 February. The source of the ESBL-KP outbreak was not identified through environmental sampling. CONCLUSIONS: Thanks to multidisciplinary management, a threatening outbreak of ESBL-KP in a NICU was controlled in few days. The prompt recognition of the event onset and the adoption of infection control interventions helped contain the bacteria spread on the ward.

Daptomycin for Treatment of S. Epidermidis Endocarditis in an Extremely Preterm Neonate-Outcome and Perspectives.

With a considerable morbidity and mortality burden, infective endocarditis still represents a challenge for clinicians. This is a case of persistent Staphylococcus epidermidis endocarditis in an extremely preterm newborn. The infection, initially treated with vancomycin, was successfully cured with daptomycin. Its use was safe and effective, ensuring a complete remission without adverse effects.

Diet in pregnant women that delivered prematurely and preterm newborn's bone status.

OBJECTIVES: Inadequate maternal dietary pattern has been associated to negative pregnancy and fetal outcomes. With this study, we aimed to evaluate the adequacy of diet in pregnant women that delivered prematurely and its possible correlations with bone status of preterm newborns. STUDY DESIGN: We prospectively enrolled women who delivered prematurely (≤than 34 gestational weeks) and their newborns (Neonatal Intensive Care, University Hospital of Padova) from January 2017 to May 2018. Maternal nutritional status and diet supplementations were assessed using a validated questionnaire. The preterm newborns were evaluated with anthropometric measurements and bone status by Quantitative Ultrasound of the second metacarpal bone within 72 h from birth. RESULTS: One hundred and eighty mothers and 202 preterm newborns were evaluated. The mothers assumed more calories, proteins, total lipids and simple sugars compared to the revised National Guidelines. The intake of calcium, phosphorus and Vitamin D was inadequate despite the use of multivitamin supplements. The mothers assumption of vitamin D and zinc positively correlated with bone status and mothers with very low intake of vitamin D during gestation (<7 µg/die) had preterm newborns with a worst bone status at birth compared to those with a better intake (>7 µg/die). CONCLUSIONS: Nutrition of pregnant women could be improved and maternal intakes of Vitamin D and zinc positively correlated with preterm newborn's bone status.

Italian neonatologists and SARS-CoV-2: lessons learned to face coming new waves.

The aim of this review was threefold: (a) to retrieve all SARS-CoV-2 evidences published by Italian neonatologists working in maternity centers and NICUs during the pandemic; (b) to summarize current evidence for the management of term and preterm infants with a SARS-CoV-2-related illness; and (c) to provide an update for dealing with the second wave of COVID-19 and discuss open questions. A review was conducted using MEDLINE/PubMed and the national COVID-19 registry of the Italian Society of Neonatology including citations from December 1, 2019 to October 28, 2020. Sixty-three articles were included. Collected data were divided into the following topics: (a) antenatal management, (b) management in delivery room, (c) postnatal management, (d) mother-baby dyad and breastfeeding management, (e) neonatal emergency transport system reorganization, (f) parents' management and perspective during SARS-CoV-2 pandemic, and (g) future perspective. Evidences have evolved over the pandemic period and the current review can be useful in the management of the mother-neonate dyad during SARS-CoV-2 future waves. Italian neonatologists have played an active role in producing official guidelines and reporting data that have contributed to improve the care of neonates. A joint European action plan is mandatory to face COVID-19 in neonates with more awareness. IMPACT: A joint European action plan is mandatory to face COVID-19 in neonates with more awareness. This review summarizes the available evidences from neonatal COVID-19 management in Italy analyzing all the published paper in this specific field of interest. The current review can be useful in the management of the mother-neonate dyad during the SARS-CoV-2 future waves.

Ultrasound for Endotracheal Tube Tip Position in Term and Preterm Infants.

BACKGROUND AND OBJECTIVE: Placing an endotracheal tube (ETT) in neonates is challenging and currently requires timely radiographic confirmation of correct tip placement. The objective was to establish the reliability of ultrasound (US) for assessing ETT position in the neonatal intensive care unit (NICU), time needed to do so, and patients' tolerance. METHODS: A prospective study on 71 newborns admitted to our NICU whose ETT placement was evaluated with US (ETT-echo) and confirmed on chest X-rays (CXR). Data were collected by 3 operators (2 neonatologists and a resident in pediatrics). The right pulmonary artery (RPA) was used as a landmark for US. The distance between the tip of the ETT and the upper margin of the RPA was measured using US and compared with the distance between the tube's tip and the carina on the CXR. RESULTS: Seventy-one intubated newborns were included in the study (n = 34 < 1,000 g, n = 18 1,000-2,000 g, n = 19 > 2,000 g). Statistical analysis (Bland-Altman plot and Lin's concordance correlation coefficient) showed an excellent consistency between ETT positions identified on US and chest X-ray. The 2 measures (ETT-echo and CXR) were extremely concordant both in the whole sample and in the subgroups. Minimal changes in patients' vital signs were infrequently observed during US, confirming the tolerability of ETT-echo. The mean time to perform US was 3.2 min (range 1-13). CONCLUSIONS: ETT-echo seems to be a rapid, tolerable, and highly reliable method worth further investigating for future routine use in neonatology with a view to reducing radiation exposure.

Trends in respiratory management of transferred very preterm infants in the last two decades.

BACKGROUND: Among infants needing urgent transfer after birth, very preterm infants are a high-risk sub-group requiring special attention. This study aimed to assess trends in early respiratory management in a large series of very preterm infants undergoing postnatal transfer. METHODS: Trends in patient characteristics and early respiratory management were assessed in 798 very preterm infants who were transferred by the Eastern Veneto Neonatal Emergency Transport Service in 2000-2019. Trends were analyzed using joinpoint regression analysis and summarized as annual percentage changes (APCs). RESULTS: Proportion of neonates with birth weight less than 1 kg decreased from 33% to 16% (APC -3.82%). Use of nasal-continuous-positive-airway pressure increased (at call: APC 15.39%; during transfer: APC 15.60%), while use of self-inflating bag (at call: APC -12.09%), oxygen therapy (at call: APC -13.00%; during transfer: APC -23.77%) and mechanical ventilation (at call: APC -2.71%; during transfer: APC -2.99%) decreased. Use of oxygen concentrations at 21% increased (at call: APC 6.26%; during transfer: APC 7.14%), while oxygen concentrations above 40% decreased (at call: APC -5.73%; at transfer APC -8.89%). Surfactant administration at call increased (APC 3%-10%), while surfactant administration when arriving at referring hospital remained around 7-11% (APC 2.55%). CONCLUSION: Relevant trends toward "gentle" approaches in early respiratory management of very preterm infants undergoing postnatal transfer occurred during the last twenty years. In addition, the proportion of transferred extremely low birth weight infants halved. Clinicians and stakeholders should consider such information when allocating assets to both hospitals and transfer services and planning regional perinatal programs.

Intra-tracheal surfactant/budesonide versus surfactant alone: Comparison of two consecutive cohorts of extremely preterm infants.

OBJECTIVES: To compare the efficacy of intra-tracheal (IT) surfactant/budesonide (SB) with that of surfactant alone (S) in reducing the rate of bronchopulmonary dysplasia (BPD) at 36 weeks post-menstrual age (PMA), we included extremely preterm very low birth weight (VLBW) infants with severe respiratory distress syndrome (RDS) in our tertiary neonatal level of care unit (Padua, Italy). STUDY DESIGN: A retrospective chart review of two cohorts of extremely preterm VLBW neonates (<28+0 gestation weeks, birth weight [BW] < 1500 g) born in two consequent epochs (2017-2018/2018-2019) were compared. The SB group received surfactant (200 mg/kg 1st dose) and budesonide (0.25 mg/kg), while the S group received surfactant alone. RESULTS: Among 68 neonates with RDS Grades III-IV, FiO2 ≥ 0.3 within 12 h of life, 18 were included in each group after matching for perinatal, clinical, and laboratory characteristics. IT SB did not affect the rate of BPD (Vermont Oxford Network, Jensen's, and National Institute of Child Health and Human Development BPD Workshop 2018 definitions), death, BPD, or death at 36 weeks PMA. Hypotension requiring inotropic support within the first 5 days was lower in those receiving the combined treatment (p = .03). The SB group had fewer admissions to pediatric ward due to respiratory causes up to 12 months of corrected age (p = .03). CONCLUSION: The preliminary results of this retrospective study suggest that in extremely preterm VLBW infants, IT SB for severe RDS did not affect the incidence of BPD, death, and BPD or death at 36 weeks PMA, compared to surfactant alone. The combined therapy proved to be safe in this population. Further studies are warranted to explore the role of early IT steroids on respiratory morbidity in preterm infants.

Untargeted and Targeted Metabolomic Profiling of Preterm Newborns with EarlyOnset Sepsis: A Case-Control Study.

Sepsis is a major concern in neonatology, but there are no reliable biomarkers for its early diagnosis. The aim of the study was to compare the metabolic profiles of plasma and urine samples collected at birth from preterm neonates with and without earlyonset sepsis (EOS) to identify metabolic perturbations that might orient the search for new early biomarkers. All preterm newborns admitted to the neonatal intensive care unit were eligible for this proof-of-concept, prospective case-control study. Infants were enrolled as "cases" if they developed EOS, and as "controls"if they did not. Plasma samples collected at birth and urine samples collected within 24 h of birth underwent untargeted and targeted metabolomic analysis using mass spectrometry coupled with ultra-performance liquid chromatography. Univariate and multivariate statistical analyses were applied. Of 123 eligible newborns, 15 developed EOS. These 15 newborns matched controls for gestational age and weight. Metabolomic analysis revealed evident clustering of the cases versus controls, with the glutathione and tryptophan metabolic pathways markedly disrupted in the former. In conclusion, neonates with EOS had a metabolic profile at birth that clearly distinguished them from those without sepsis, and metabolites of glutathione and tryptophan pathways are promising as new biomarkers of neonatal sepsis.

Optimizing Nutritional Strategies to Prevent Necrotizing Enterocolitis and Growth Failure after Bowel Resection.

Necrotizing enterocolitis (NEC), the first cause of short bowel syndrome (SBS) in the neonate, is a serious neonatal gastrointestinal disease with an incidence of up to 11% in preterm newborns less than 1500 g of birth weight. The rate of severe NEC requiring surgery remains high, and it is estimated between 20-50%. Newborns who develop SBS need prolonged parenteral nutrition (PN), experience nutrient deficiency, failure to thrive and are at risk of neurodevelopmental impairment. Prevention of NEC is therefore mandatory to avoid SBS and its associated morbidities. In this regard, nutritional practices seem to play a key role in early life. Individualized medical and surgical therapies, as well as intestinal rehabilitation programs, are fundamental in the achievement of enteral autonomy in infants with acquired SBS. In this descriptive review, we describe the most recent evidence on nutritional practices to prevent NEC, the available tools to early detect it, the surgical management to limit bowel resection and the best nutrition to sustain growth and intestinal function.

Variability in the management and imaging use in paediatric minor head trauma in European emergency departments. A Research in European Pediatric Emergency Medicine study.

OBJECTIVE: The objective of the study was to assess the variability in the management of paediatric MHT in European emergency departments (EDs). METHODS: This was a multicentre retrospective study of children ≤18 years old with minor head trauma (MHT) (Glasgow Coma Scale ≥14) who presented to 15 European EDs between 1 January 2013 and 31 December 31. Data on clinical characteristics, imaging tests, and disposition of included patients were collected at each hospital over a 3-year period. RESULTS: We included 11 212 patients. Skull radiography was performed in 3416 (30.5%) patients, range 0.4-92.3%. A computed tomography (CT) was obtained in 696 (6.2%) patients, range 1.6-42.8%. The rate of admission varied from 0 to 48.2%. CONCLUSION: We found great variability in terms of the type of imaging and rate of CT scan obtained. Our study suggests opportunity for improvement in the area of paediatric head injury and the need for targeted individualised ED interventions to improve management of MHT.

Intrauterine Growth Restriction: New Insight from the Metabolomic Approach.

Recognizing intrauterine growth restriction (IUGR) is a matter of great concern because this condition can significantly affect the newborn's short- and long-term health. Ever since the first suggestion of the "thrifty phenotype hypothesis" in the last decade of the 20th century, a number of studies have confirmed the association between low birth weight and cardiometabolic syndrome later in life. During intrauterine life, the growth-restricted fetus makes a number of hemodynamic, metabolic, and hormonal adjustments to cope with the adverse uterine environment, and these changes may become permanent and irreversible. Despite advances in our knowledge of IUGR newborns, biomarkers capable of identifying this condition early on, and stratifying its severity both pre- and postnatally, are still lacking. We are also still unsure about these babies' trajectory of postnatal growth and their specific nutritional requirements with a view to preventing, or at least limiting, long-term complications. In this setting, untargeted metabolomics-a relatively new field of '-omics' research-can be a good way to investigate the metabolic perturbations typically associated with IUGR. The aim of this narrative review is to provide a general overview of the pathophysiological and clinical aspects of IUGR, focusing on evidence emerging from metabolomic studies. Though still only preliminary, the reports emerging so far suggest an "early" pattern of glucose intolerance, insulin resistance, catabolite accumulation, and altered amino acid metabolism in IUGR neonates. Further, larger studies are needed to confirm these results and judge their applicability to clinical practice.

Innate immunity ascertained from blood and tracheal aspirates of preterm newborn provides new clues for assessing bronchopulmonary dysplasia.

AIM: The study aimed to establish how granulocytes, monocytes and macrophages contribute to the development of bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS: Study A: samples of blood and tracheal aspirates (TAs) collected from preterm newborn infants during the first 3 days of life were investigated by flow cytometry, and testing for white blood cells (WBCs), neutrophils and neutrophil extracellular traps (NETs). Maternal blood samples were also collected. Study B: data from previously-tested samples of TAs collected from preterm newborn infants were re-analyzed in the light of the findings in the new cohort. RESULTS: Study A: 39 preterm newborn infants were studied. A moderate correlation emerged between maternal WBCs and neutrophils and those of their newborn in the first 3 days of life. WBCs and neutrophils correlated in the newborn during the first 8 days of life. Decision rules based on birth weight (BW) and gestational age (GA) can be used to predict bronchopulmonary dysplasia (BPD). Neutrophil levels were lower in the TAs from the newborn with the lowest GAs and BWs. Study B: after removing the effect of GA on BPD development, previously-tested newborn were matched by GA. Monocyte phenotype 1 (Mon1) levels were lower in the blood of newborn with BPD, associated with a higher ratio of Monocyte phenotype 3 (Mon3) to Mon1. Newborn infants from mothers with histological chorioamnionitis (HCA) had lower levels of classically-activated macrophages (M1) and higher levels of alternatively-activated macrophages (M2) in their TAs than newborn infants from healthy mothers. CONCLUSION: Immune cell behavior in preterm newborn infants was examined in detail. Surprisingly, neutrophil levels were lower in TAs from the newborn with the lowest GA and BW, and no correlation emerged between the neutrophil and NET levels in TAs and the other variables measured. Interestingly, monocyte phenotype seemed to influence the onset of BPD. The rise in the ratio of Mon 3 to Mon 1 could contribute to endothelial dysfunction in BPD.

Restricted Palivizumab Recommendations and the Impact on RSV Hospitalizations among Infants Born at > 29 Weeks of Gestational Age: An Italian Multicenter Study.

OBJECTIVE: Premature infants have the highest risk of being hospitalized with respiratory syncytial virus (RSV) infections. Palivizumab is the only licensed agent for RSVhospitalization (RSVH) prophylaxis in infants born at < 35 weeks of gestational age (wGA). In 2016, the Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) has restricted the eligibility for reimbursement to infants at high risk of RSVH, ruling out palivizumab administration for infants born at > 29 wGA. The aim of the present study was to compare the incidence of RSVH in two consecutive epidemic seasons (2015-2016 vs. 2016-2017), that is, before and after the new AIFA recommendations on palivizumab eligibility. STUDY DESIGN: This was a noninterventional retrospective cohort study conducted at three neonatal intensive care units (NICUs) in northern Italy. Infants born at 29 and 35 wGA between March 15, 2015 and March 14, 2017 were enrolled for this study. Electronic medical charts were reviewed and parents were interviewed by telephone. Data were collected on neonatal course during NICU stay, palivizumab administration, and hospitalizations related to respiratory infections during the 1st year of life, comparing the infants born in season 1 with season 2. RESULTS: Of 632 eligible infants, data were available for 536 (262 in season 1 and 274 in season 2). Overall, RSVH occurred 1.9 and 5.1% in infants in seasons 1 and 2, respectively (odds ratio [OR] = 2.77; 95% confidence interval [CI]: 0.98-7.8, p = 0.045). When the analysis was limited to patients not exposed to palivizumab, RSVHs were recorded for 1.8 and 5.9% infants in seasons 1 and 2, respectively (OR = 3.42; 95% CI: 0.96-12.20, p = 0.045). It is noteworthy that the incidence of hospital admissions for respiratory viruses other than RSV did not differ between the two seasons. CONCLUSION: Restricting eligibility for palivizumab reimbursement led to a significant increase in RSVH but had no impact on hospitalizations for other respiratory viruses. Future decisions on palivizumab prescription and coverage rules should be driven by a careful assessment of the cost-benefit ratio.