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.

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.

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.

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.

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.

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.

Surfactant Components and Tracheal Aspirate Inflammatory Markers in Preterm Infants with Respiratory Distress Syndrome.

In 93 preterm infants ≤32 weeks of gestational age and 12 control infants, epithelial lining fluid disaturated-phosphatidylcholine, surfactant protein A and B, albumin, and myeloperoxidase activity were assessed after intubation and before exogenous surfactant administration. We found that disaturated-phosphatidylcholine, surfactant protein B, and myeloperoxidase were significantly higher in preterms with chorioamnionitis.

Neonatal independent predictors of severe NEC.

PURPOSE: Necrotizing enterocolitis (NEC) is a severe neonatal disease. The present study aimed to identify factors predisposing the development of severe forms of NEC. METHODS: This retrospective study examined NEC patients in a single centre between 2002 and 2015. Data concerning clinical characteristics, therapeutic management as well as short-term outcomes were collected. We compared the patients receiving successful medical treatment and those requiring surgical intervention. Patients who underwent surgery were distinguished in three subcategories. Bivariate and multivariate analyses were used for the statistical analysis. RESULTS: We identified 155 patients in the study period. 102 were treated conservatively and 53 required surgery. 8 received a primary peritoneal drainage, 31 received a drainage and a subsequent laparotomy and 14 received a laparotomy. Multivariate regression analysis identified a lower risk for surgery with a later onset and higher serum pH values, whereas an increased risk with higher C reactive Protein (CRP) levels at the onset. Pneumatosis intestinalis was identified as a protective factor. Overall mortality was 6.4%, with higher percentage in surgical NEC. CONCLUSION: This study suggests that a later onset is a protective sign for the progression to surgery, whereas lower pH values and higher CRP levels are prognostic factors associated with the need for surgery. The line of treatment involving explorative laparotomy in case of perforation seems to be rewarded by low morbidity and mortality rate.

RSV infection and respiratory sequelae.

INTRODUCTION: The association between respiratory syncytial virus (RSV) infections and long-term respiratory sequelae has long been recognized. It is estimated that individuals with a history of RSV bronchiolitis have 2- to 12-fold higher risk of developing asthma. Although this risk tends to decrease with age, persistent airway obstruction and hyperresponsiveness are observed even 30 years after RSV infection. EVIDENCE ACQUISITION: Our data search strategy was designed to address the following questions: What is the epidemiological evidence available on the association between RSV infection and long-term respiratory morbidity? What are the potential pathogenic pathways linking RSV infection to long-term respiratory morbidity? Are there any host genetic backgrounds that can predispose to both severe RSV lower respiratory tract infection and asthma? Are antiviral therapies and RSV prevention measures effective in reducing respiratory morbidities? EVIDENCE SYNTHESIS: This article reviews the recent scientific literature on the epidemiological association and pathogenic links between early RSV infection and long-term respiratory morbidities. CONCLUSIONS: Nowadays, asthma is increasingly considered a heterogeneous disease, caused by interactions between several host and environmental factors. Understanding the specific causative role of respiratory viruses, and the pathogenic mechanisms through which bronchiolitis predisposes to asthma, is a challenging, but essential starting point for the development of prevention and treatment strategies potentially capable of preserving lung function.

Heated, Humidified High-Flow Nasal Cannulae as a Form of Noninvasive Respiratory Support for Preterm Infants and Children with Acute Respiratory Failure.

Heated, humidified high-flow delivered by nasal cannulae (HHHFNC) is increasingly used for noninvasive respiratory support in preterm infants and critically ill children due to its perceived effectiveness and ease of use. Evidence from randomized controlled trials suggests that HHHFNC and continuous positive airway pressure (CPAP) are equally effective as postextubation support in preterm infants. HHHFNC is also used for weaning preterm infants from CPAP. Data on HHHFNC used as the primary support for treating respiratory distress syndrome are conflicting. HHHFNC use in preterm infants is associated with reduced nasal trauma. Inability to measure the pressure generated by HHHFNC systems is a concern because overexpansion can lead to an air leak and lung injury. Great caution is warranted when HHHFNC is used in extremely low-birth-weight infants (who were rarely included in these randomized controlled trials) because a recent retrospective study found its use is associated with a higher likelihood of bronchopulmonary dysplasia or death in this population. HHHFNC has also become popular in pediatric intensive care units and pediatric wards as a method for delivering oxygen and noninvasive respiratory support. Most published studies were conducted on infants and young children with bronchiolitis. The results of a few observational studies and two randomized trials suggest that HHHFNC therapy is effective in the treatment of bronchiolitis. This review discusses the proposed mechanisms of action behind HHHFNC, the results of observational studies, and the evidence emerging from clinical trials on the use of HHHFNC in preterm infants and children critically ill with bronchiolitis.

Respiratory Outcome after Preterm Birth: A Long and Difficult Journey.

Despite notable advances in the survival and management of preterm infants in recent decades, chronic lung disease remains a common complication. Approximately one in three infants born preterm (< 32 weeks of gestation) are hospitalized with respiratory problems (mainly due to infections) in their first 2 years of life, and the risk of childhood wheezing is three times higher in this population. By comparison with infants born at term, there seems to be a higher incidence of respiratory morbidity in those born preterm, even in the absence of bronchopulmonary dysplasia (BPD) and in late-preterm babies. Although long-term follow-up data are still not collected systematically, there is evidence of preterm infants' respiratory symptoms, lung function impairments, and radiological abnormalities, tending to persist throughout childhood and into early adulthood. Respiratory conditions associated with preterm birth are often diagnosed and treated as asthma, but the pathophysiological patterns of BPD and asthma are very different. Future research should focus on characterizing preterm infants' pathological pulmonary features by gestational age at birth, and presence or absence of BPD. Improving our current knowledge of the respiratory disorder associated with prematurity might hopefully prompt targeted follow-up protocols, and novel prevention strategies and treatment approaches.

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.

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.

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.

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.

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.

Brain and spine MRI features of Hunter disease: frequency, natural evolution and response to therapy.

BACKGROUND: Hunter disease is a rare X-linked mucopolysaccharidosis. Despite frequent neurological involvement, characterizing the severe phenotype, neuroimaging studies are scarce. OBJECTIVES: To determine frequency and severity of neuroradiological mucopolysaccharidosis-related features; to correlate them with clinical phenotype; to evaluate their natural evolution and the impact of intravenous enzymatic replacement therapy (ERT). METHODS: Sixty nine brain MRI examinations of 36 Italian patients (mean-age 10.4 years; age-range 2.2-30.8; severe phenotype in 22 patients) were evaluated. Twenty patients had multiple MRIs (median follow-up 3.1 years, range 1-16.9): among them 15 had MRIs before and after ERT, six had repeated MRIs without being on ERT and five while on ERT. Perivascular, subarachnoid and ventricle space enlargement, white matter abnormality (WMA) burden, pituitary sella/skull/posterior fossa abnormalities, periodontoid thickening, spinal stenosis, dens hypoplasia, myelopathy, vertebral and intervertebral disc abnormalities were graded by means of dedicated scales. RESULTS: Perivascular spaces enlargement (89%), WMAs (97%), subarachnoid space enlargement (83%), IIIrd-ventricle dilatation (100%), pituitary sella abnormalities (80%), cranial hyperostosis (19%), craniosynostosis (19%), enlarged cisterna magna (39%), dens hypoplasia (66%), periodontoid thickening (94%), spinal stenosis (46%), platyspondylia (84%) and disc abnormalities (79%) were frequently detected. WMAs, IIIrd-ventricle dilatation and hyperostosis correlated with the severe phenotype (p < 0.05). Subarachnoid spaces and ventricle enlargement, WMAs and spinal stenosis progressed despite ERT, while other MR features showed minimal or no changes. CONCLUSIONS: The spectrum of brain and spine MRI abnormalities in Hunter disease is extremely wide and requires a thorough evaluation. WMAs, atrophy/communicating hydrocephalus and spinal stenosis progress over time and might represent possible disease severity markers for new treatment efficacy assessment.

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.

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.