Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis.

ABSTRACT: In physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPCs) are present in the peripheral blood, but their contribution to human hematopoiesis remain unsolved. By integrating advanced immunophenotyping, single-cell transcriptional and functional profiling, and integration site (IS) clonal tracking, we unveiled the biological properties and the transcriptional features of human cHSPC subpopulations in relationship to their bone marrow (BM) counterpart. We found that cHSPCs reduced in cell count over aging and are enriched for primitive, lymphoid, and erythroid subpopulations, showing preactivated transcriptional and functional state. Moreover, cHSPCs have low expression of multiple BM-retention molecules but maintain their homing potential after xenotransplantation. By generating a comprehensive human organ-resident HSPC data set based on single-cell RNA sequencing data, we detected organ-specific seeding properties of the distinct trafficking HSPC subpopulations. Notably, circulating multi-lymphoid progenitors are primed for seeding the thymus and actively contribute to T-cell production. Human clonal tracking data from patients receiving gene therapy (GT) also showed that cHSPCs connect distant BM niches and participate in steady-state hematopoietic production, with primitive cHSPCs having the highest recirculation capability to travel in and out of the BM. Finally, in case of hematopoietic impairment, cHSPCs composition reflects the BM-HSPC content and might represent a biomarker of the BM state for clinical and research purposes. Overall, our comprehensive work unveiled fundamental insights into the in vivo dynamics of human HSPC trafficking and its role in sustaining hematopoietic homeostasis. GT patients' clinical trials were registered at ClinicalTrials.gov (NCT01515462 and NCT03837483) and EudraCT (2009-017346-32 and 2018-003842-18).

Early respiratory system reactance predicts respiratory outcomes in preterm infants: a retrospective, multicentre study.

OBJECTIVE: This multicenter, international, retrospective study aims to investigate whether respiratory system reactance (Xrs) assessed by respiratory oscillometry on the 7th day of life is associated with respiratory outcomes in preterm infants below 32 weeks' gestation. METHODS: Sinusoidal pressure oscillations (2-5 cmH2O peak-to-peak, 10 Hz) were superimposed on the positive end-expiratory pressure (PEEP). We assessed the association of Xrs z-score with the duration of respiratory support using linear regression and with bronchopulmonary dysplasia (BPD, according to Jensen et al. 2019) using logistic regression. We used the likelihood ratio test to evaluate whether Xrs z-score adds significantly to clinical predictors, including gestational age (GA), birth weight (BW) and the National Institute of Child Health and Human Development (NICHD) BPD prediction model. RESULTS: One hundred and thirty-seven infants (median (Q1, Q3) GA=28.43 (26.11, 30.29) weeks) were included; 44 (32%) developed BPD. Xrs z-score was significantly associated with the duration of respiratory support (R2=0.35). Xrs z-score was significantly higher in infants who developed BPD (p<0.001); the optimal cut-off value was 2.6, associated with 77% sensitivity and 80% specificity. In univariable analysis, per z-score increase in Xrs, the OR for BPD increased by 60% and the respiratory support by eight days. In multivariable analysis, Xrs z-score added significantly to the NICHD model and to GA and BW z-score to predict respiratory support duration (p=0.016 and p=0.014, respectively) and BPD development (p=0.003 and p<0.001, respectively). CONCLUSION: Xrs z-score on the 7th day after birth improves the prediction of respiratory outcome in preterm infants.

Estimation of the reference values and decision limits for growth hormone in newborns using dried blood spots.

OBJECTIVES: Severe deficiency of growth hormone (GHD) of the newborn is a rare but potentially life-threatening disease. GH measured during the first week of life, using dried blood spots (DBS), may offer several advantages. Aim of the study was to estimate the reference values for GH in newborns by a new analytical method using DBS. METHODS: Using a new developed analytical method, GH was estimated from DBS of 1,036 healthy newborns attending the Neonatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan in the period July-October 2021. Reference values for GH deficiency were estimated by the Harrell-Davis bootstrap method, with 90 %CI calculated by the bias-corrected and accelerated bootstrap method. RESULTS: All GH measurements required 33 analytical sessions (8 months) with a CV% for calibration curve slopes equal to 6.9 %. Intermediate precision evaluated by measurement of low (3 µg/L) and high (10 µg/L) quality controls was, respectively, 14 and 6.5 %. GH reference values, estimated at percentiles 1.0st, 2.5th and 5.0th, and their 90 %CI, were, respectively, 4.5 µg/L (90 %CI 3.8-5.1), 5.9 µg/L (90 %CI 5.4-6.4) and 7.0 µg/L (90 %CI 6.7-7.3). GH levels were not associated with sex, standard deviation scores, birth weight, gestational age, type of delivery or mother's variables (age, smoking habit, gestational diabetes). CONCLUSIONS: Validation data suggest that this method can be used to measured GH in newborns using DBS. The reference values estimated in this study are in accordance with previous published works using ELISA and may help confirming the clinical suspicion of neonatal GHD.

Retrospective study on neonatal seizures in a tertiary center of northern Italy after ILAE classification: Incidence, seizure type, EEG and etiology.

OBJECTIVE: We aimed to evaluate epidemiology, seizure type, EEG, and etiology of neonatal seizures (NS) in a tertiary neonatal intensive care unit. METHODS: Data on infants with a neurophysiological confirmation of NS were collected between 2009 and 2022. Seizure types and epileptic syndromes were classified by the ILAE classification and EEG by the Italian Neonatal Seizure Collaborative Network (INNESCO) score. RESULTS: Out of 91,253 neonates, 145 presented with NS; 69.7 % were born at term and 30.3 % were preterm infants. The incidence of NS in neonates born at our center was 1.2 per 1,000 live newborns (96/80697 neonates) while in the entire neonatal population admitted to our center it was 1.6 per 1,000 live births, increasing with lower preterm age. Compared to previous studies, we found a lower proportion of hypoxic-ischemic encephalopathy (HIE) (23.4 %) and a higher rate of genetic contribution (26.2 %). The infection rate was higher in preterm (31.8 %) than in full term (9.9 %) infants. Electrographic seizures were associated with acute provoked seizures (35.9 %), preterm age (52.3 %), and HIE (52.9 %). Vascular etiology was associated with focal clonic seizures (56.8 %). Non-structural neonatal genetic epilepsy was associated with sequential seizures (68.2 %), particularly KCNQ2 and SCN2A epilepsy. Background EEG was abnormal in all HIE, infections (85.7 %) and metabolic NS (83.3 %). In genetic epilepsy, background EEG depended on the epileptic syndrome: normal in 80 % of self-limited neonatal epilepsy and abnormal in 77.8 % of developmental and epileptic encephalopathy. Electroclinical seizures were associated with focal onset, while electrographic seizures correlated with a multifocal onset. CONCLUSIONS: A low incidence of HIE and a high incidence of genetic etiology were observed in our cohort of NS. Seizure type and EEG features are fundamental to address etiology.

Congenital diaphragmatic hernia: automatic lung and liver MRI segmentation with nnU-Net, reproducibility of pyradiomics features, and a machine learning application for the classification of liver herniation.

Prenatal assessment of lung size and liver position is essential to stratify congenital diaphragmatic hernia (CDH) fetuses in risk categories, guiding counseling, and patient management. Manual segmentation on fetal MRI provides a quantitative estimation of total lung volume and liver herniation. However, it is time-consuming and operator-dependent. In this study, we utilized a publicly available deep learning (DL) segmentation system (nnU-Net) to automatically contour CDH-affected fetal lungs and liver on MRI sections. Concordance between automatic and manual segmentation was assessed by calculating the Jaccard coefficient. Pyradiomics standard features were then extracted from both manually and automatically segmented regions. The reproducibility of features between the two groups was evaluated through the Wilcoxon rank-sum test and intraclass correlation coefficients (ICCs). We finally tested the reliability of the automatic-segmentation approach by building a ML classifier system for the prediction of liver herniation based on support vector machines (SVM) and trained on shape features computed both in the manual and nnU-Net-segmented organs. We compared the area under the classifier receiver operating characteristic curve (AUC) in the two cases. Pyradiomics features calculated in the manual ROIs were partly reproducible by the same features calculated in nnU-Net segmented ROIs and, when used in the ML procedure, to predict liver herniation (both AUC around 0.85).          Conclusion: Our results suggest that automatic MRI segmentation is feasible, with good reproducibility of pyradiomics features, and that a ML system for liver herniation prediction offers good reliability.          Trial registration: https://clinicaltrials.gov/ct2/show/NCT04609163?term=NCT04609163&draw=2&rank=1 ; Clinical Trial Identification no. NCT04609163. What is Known: • Magnetic resonance imaging (MRI) is crucial for prenatal congenital diaphragmatic hernia (CDH) assessment. It enables the quantification of the total lung volume and the extent of liver herniation, which are essential for stratifying the severity of CDH, guiding counseling, and patient management. • The manual segmentation of MRI scans is a time-consuming process that is heavily reliant upon the skill set of the operator. What is New: • MRI lung and liver automatic segmentation using the deep learning nnU-Net system is feasible, with good Jaccard coefficient values and satisfactory reproducibility of pyradiomics features compared to manual results. • A feasible ML system for predicting liver herniation could improve prenatal assessments and CDH patient management.

Exclusive human milk feeding and prevalence of early adiposity rebound in ELBW infants: a retrospective cohort study.

The purpose of the present study was to evaluate the prevalence of early adiposity rebound (EAR) and factors associated with its occurrence in a cohort of extremely low birth weight infants (ELBW). We conducted a retrospective longitudinal study including ELBW infants followed-up for up to 10 years after discharge. EAR was defined as occurring before 5 years of age. A multivariate binary logistic regression analysis was performed to evaluate maternal and perinatal variables independently associated with EAR. Out of 212 ELBW infants included in the analysis, 40.6% developed EAR and 21.5% showed it before 4 years of age. Only formula milk feeding at discharge was independently associated with a higher risk of EAR. The mean BMI of children with EAR was higher than that of children without EAR. Furthermore, the prevalence of overweight and obesity was higher in the EAR group than in the timely AR group.  Conclusions: ELBW infants in our cohort developed EAR in a relatively high percentage of cases. In this already at-risk population, EAR may represent a further risk factor for an adverse metabolic outcome. Monitoring preterm infants' growth within a long-term follow-up program and promoting and supporting human milk feeding is advisable. What is Known: • Preterm-born infants are at high risk for long-term adverse health outcomes, especially cardiovascular and metabolic. • The occurrence of early adiposity rebound (EAR) is associated with the risk of later obesity and metabolic syndrome. What is New: • The occurrence of EAR in ELBW infants may represent an additional risk factor for later adverse metabolic outcomes in an already vulnerable population. • Future preventive strategies should include a long-term follow-up and the promotion of exclusive breastfeeding.

Long-lasting effects of COVID-19 pandemic on hospitalizations and severity of bronchiolitis.

Bronchiolitis is a common cause of hospitalization in infants. The long-lasting impact of hygiene and social behavior changes during the pandemic on this disease is debated. We investigated the prevalence of hospitalized cases, clinical severity, and underlying risk factors before and during pandemic. The study was conducted in 27 hospitals in Italy and included infants hospitalized for bronchiolitis during the following four periods: July 2018-March 2019, July 2020-March 2021, July 2021-March 2022, and July 2022-March 2023. Data on demographics, neonatal gestational age, breastfeeding history, underlying chronic diseases, presence of older siblings, etiologic agents, clinical course and outcome were collected. A total of 5330 patients were included in the study. Compared to 2018-19 (n = 1618), the number of hospitalizations decreased in 2020-21 (n = 121). A gradual increase was observed in 2021-22 (n = 1577) and 2022-23 (n = 2014). A higher disease severity (need and length of O2-supplementation, need for non-invasive ventilation, hospital stay) occurred in the 2021-22 and, especially, the 2022-23 periods compared to 2018-19. This tendency persisted after adjusting for risk factors associated with bronchiolitis severity.   Conclusions: Compared to adults, COVID-19 in infants is often asymptomatic or mildly symptomatic and rarely results in hospitalization. This study indicates that the pandemic has indirectly induced an increased burden of bronchiolitis among hospitalized infants. This shift, which is not explained by the recognized risk factors, suggests the existence of higher infant vulnerability during the last two seasons. What is known: • The pandemic led to a change in epidemiology of respiratory diseases • Large data on severity of bronchiolitis and underlying risk factors before and during COVID-19 pandemic are scarce What is new: • Compared to pre-pandemic period, hospitalizations for bronchiolitis decreased in 2020-21 and gradually increased in 2021-22 and 2022-23 • Compared to pre-pandemic period, higher disease burden occurred in 2021-22 and, especially, in 2022-23. This tendency persisted after adjusting for risk factors associated with bronchiolitis severity • The interplay among viruses, preventive measures, and the infant health deserves to be further investigated.

Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey.

Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian neonatal units. A prospective cross-sectional study was conducted in Italian and Spanish neonatal units using a web-based survey with 43 questions. A modified Delphi method involved experts refining the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices. CONCLUSIONS: The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in neonatal units. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe. WHAT IS KNOWN: • Neonates in intensive care face a high risk of nephrotoxicity and ototoxicity from drugs like aminoglycosides, vancomycin, loop diuretics, and ibuprofen. • Therapeutic drug monitoring is key for managing these risks, optimizing dosing for efficacy and minimizing side effects. WHAT IS NEW: • NICUs in Spain and Italy show high drug toxicity awareness but differ in ototoxic/nephrotoxic drug management. • Urgent need for standard guidelines and practices to address nephrotoxic risks from aminoglycosides, vancomycin, loop diuretics, and ibuprofen.

Can Postbiotics Represent a New Strategy for NEC?

Intestinal bacteria, also known as gut microbiota, are a rich ecology of microorganisms found in the human digestive tract. Extensive study has highlighted their critical relevance in preserving human health. New research has revealed that bacterial viability is not invariably necessary to induce health benefits. Postbiotics (defined soluble substances produced as a byproduct of the metabolic processes of living microbes) have thus emerged as an important topic of research. They contribute to shaping the gut microbiota, exert immune-modulation activity, and improve the integrity of the gut barrier.Alterations in preterm gut colonization associated with intestinal barrier immaturity and the increased reactivity of the intestinal mucosa to colonizing bacteria have been implicated in the pathogenesis of necrotizing enterocolitis. Postbiotics have shown promising outcomes in reducing the risk of developing NEC, lowering inflammation, encouraging the development of good bacteria, and strengthening the intestinal barrier. This is an important advancement in newborn care and highlights the potential of postbiotics to avoid severe intestinal disorders.

Chung-Jansen syndrome can mimic Cornelia de Lange syndrome: Another player among chromatinopathies?

Cornelia de Lange syndrome (CdLS) is a rare multisystem congenital neurodevelopmental disorder (NDD) characterized by distinctive facial anomalies, short stature, developmental delay, hirsutism, gastrointestinal abnormalities and upper limb reduction defects. CdLS syndrome is associated with causative variants in genes encoding for the cohesin complex, a cellular machinery involved in chromatid pairing, DNA repair and gene-expression regulation. In this report, we describe a familial case of a syndromic presentation in a 4-year-old patient (P1) and in his mother (P2). Trio-based Whole Exome Sequencing (WES) performed on P1 was first negative. Since his phenotypic evolution during the follow-up was reminiscent of the CdLS spectrum, a reanalysis of WES data, focused on CdLS-related genes, was requested. Although no alterations in those genes was detected, we identified the likely pathogenetic variant c.40G > A (p.Glu14Lys) in the PHIP gene, in the meanwhile associated with Chung-Jansen syndrome. Reverse phenotyping carried out in both patients confirmed the molecular diagnosis. CHUJANS belongs to NDDs, featuring developmental delay, mild-to-moderate intellectual disability, behavioral problems, obesity and facial dysmorphisms. Moreover, as here described, CHUJANS shows a significant overlap with the CdLS spectrum, with specific regard to facial gestalt. On the basis of our findings, we suggest to include PHIP among genes routinely analyzed in patients belonging to the CdLS spectrum.

Postnatal growth of small for gestational age late preterm infants: determinants of catch-up growth.

BACKGROUND: Failure to recover growth is a risk reported in late preterm population. This study aimed to evaluate the auxological outcome of late preterm infants and identify factors associated with failure to recover growth. METHODS: We enrolled late preterm infants with birth weight ≤10th percentile, followed up at High-Risk Infant Follow-up Service. We collected data at birth and at follow-up visits. A logistic regression analysis was performed to assess variables independently associated with growth failure. RESULTS: The population consisted of 175 preterms. The percentage of children showing no weight recovery was 34% at 36 months. At logistic regression analysis, infants who had not regained weight at 12 months had a higher risk of not regaining weight even at 36 months. The same risk factor was highlighted for length catch-up growth. Moreover, infants fed any human milk at discharge were protected from not achieving both weight and length catch-up growth at 36 months. CONCLUSION: These results indicate that children born late preterm and small for gestational age could fail to recover weight and stature growth in the first 36 months. The protective effect of human milk on failure to thrive highlights the importance of promoting breastfeeding in this population. IMPACT: A significant number of SGA late preterms show a failure to recover weight and statural growth. Having experienced intrauterine growth restriction is associated with a greater chance of achieving statural catch-up growth. Being born singleton represents a risk factor for slower weight and height growth velocity. Breastmilk has a protective effect on failure to recover adequate weight and length in preterm SGA infants. This finding highlights the importance of promoting breastfeeding in this population.

A novel echocardiography method to assess upper body systemic blood flow in preterm infants and comparison with superior vena cava flow measurement.

To evaluate feasibility, reproducibility, and prognostic value of a new echocardiographic method to assess systemic arterial blood flow directed to the upper part of the body (UBAF, upper body arterial flow) alternative to superior vena cava flow (SVCF) measurement. We performed echocardiographic evaluations in 106 infants in the first 2 days of life to obtain SVCF, left ventricle output (LVO), UBAF, and standard parameters of patent ductus arteriosus (PDA) significance. UBAF was calculated by subtracting from LVO the aortic arch blood flow measured immediately distally to the origin of the left subclavian artery. Main outcome measures: UBAF and SVCF agreement was assessed by Bland-Altman analysis in terms of bias, limits of agreement and repeatability index. The Intraclass Correlation Coefficient was used to measure the strength of inter-rater agreement. The agreement between UBAF and SVCF was high. The Concordance Correlation Coefficient (CCC) was 0.7434. (CCC 0.7434, 95% C.I. [0.656, 0.8111]). There was a good absolute agreement between the two raters ICC = 0.747; p value < 0.0001; 95%CI [0.601; 0.845]. Adjusting for confounding factors (BW, GA, PDA) included in the model, there was a statistically significant relationship between UBAF and SVCF. CONCLUSION: UBAF showed a strong agreement with the SCVF with a better reproducibility. Our data support UBAF as a potentially useful marker of cerebral perfusion in the evaluation of preterm infants. WHAT IS KNOWN: • Low SVC (superior vena cava) flow in the neonatal period has been associated with periventricular haemorrhage and unfavourable long-term neurodevelopmental outcome. • Ultrasound measurement of flow in SVC shows relatively high inter-operator variability. WHAT IS NEW: • Our study highlights how much overlap there is between upper-body arterial flow (UBAF) measurement and SCV flow measurement. UBAF is easier to perform and has a strong correlation with better reproducibility. • UBAF may replace measurement of cava flow as a method for haemodynamic monitoring of unstable preterm and asphyxiated infants.

Dose-dependent impact of human milk feeding on tidal breathing flow-volume loop parameters across the first 2 years of life in extremely low-birth-weight infants: a cohort study.

The purpose of this study is to test the hypothesis that higher consumption of human milk (HM) in preterm infants with birth weight (BW) <1000 g is associated with improved lung function in a dose-dependent manner over the first 2 years of corrected age (CA). This retrospective study at an academic medical center included infants with BW <1000g. They had lung function assessment by the tidal breathing flow-volume loop (TBFVL) follow-up visits at 0-3-, 3-6-, 6-12-, 12-18-, and 18-24-month CA. One hundred eighty infants were included in the study with a mean (SD) gestational age 26.5 (1.90) weeks and BW 772.4 (147.0) g, 50% were female, and 60% developed BPD. 62.8% of infants received HM during the NICU stay. According to a general linear model (including GA, being small for GA (SGA), sex, human milk percentage, sepsis, and BPD), on average, each week of GA resulted in a higher tPTEF/tE of 1.24 (p = 0.039) and being SGA in a lower tPTEF/tE of 5.75 (p = 0.013) at 0-3-month CA. A higher percentage of human milk out of the total enteral intake was associated with better tPTEF/tE z-scores at 0-3 months (p = 0.004) and 18-24 months of CA (p = 0.041). BPD diagnosis was associated with a relevantly worse tPTEF/tE z-score at 6-12 months of CA (p = 0.003). CONCLUSION: Preterm infants with higher consumption of HM had significantly less airway obstruction across the first 2 years, suggesting that human milk may contribute in a dose-dependent manner to improve lung function in early childhood in former preterm infants born ELBW. WHAT IS KNOWN: • Human milk feeding reduces the risk of prematurity-related morbidities, including necrotizing enterocolitis, sepsis, lower respiratory tract infections, and BPD. Both exclusive and partial human milk feeding appear to be associated with a lower risk of BPD in preterm infants. WHAT IS NEW: • This cohort study of 180 preterm infants with birth weight < 1000 g found that exposure to human milk during hospitalization improves airway obstruction markers tPTEF/tE z-score over the first 2 years of corrected age in a dose-dependent manner.

Variation in delivery room management of preterm infants across Europe: a survey of the Union of European Neonatal and Perinatal Societies.

The aim of the present study, endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Italian Society of Neonatology (SIN), was to analyze the current delivery room (DR) stabilization practices in a large sample of European birth centers that care for preterm infants with gestational age (GA) < 33 weeks. Cross-sectional electronic survey was used in this study. A questionnaire focusing on the current DR practices for infants < 33 weeks' GA, divided in 6 neonatal resuscitation domains, was individually sent to the directors of European neonatal facilities, made available as a web-based link. A comparison was made between hospitals grouped into 5 geographical areas (Eastern Europe (EE), Italy (ITA), Mediterranean countries (MC), Turkey (TUR), and Western Europe (WE)) and between high- and low-volume units across Europe. Two hundred and sixty-two centers from 33 European countries responded to the survey. At the time of the survey, approximately 20,000 very low birth weight (VLBW, < 1500 g) infants were admitted to the participating hospitals, with a median (IQR) of 48 (27-89) infants per center per year. Significant differences between the 5 geographical areas concerned: the volume of neonatal care, ranging from 86 (53-206) admitted VLBW infants per center per year in TUR to 35 (IQR 25-53) in MC; the umbilical cord (UC) management, being the delayed cord clamping performed in < 50% of centers in EE, ITA, and MC, and the cord milking the preferred strategy in TUR; the spotty use of some body temperature control strategies, including thermal mattress mainly employed in WE, and heated humidified gases for ventilation seldom available in MC; and some of the ventilation practices, mainly in regard to the initial FiO2 for < 28 weeks' GA infants, pressures selected for ventilation, and the preferred interface to start ventilation. Specifically, 62.5% of TUR centers indicated the short binasal prongs as the preferred interface, as opposed to the face mask which is widely adopted as first choice in > 80% of the rest of the responding units; the DR surfactant administration, which ranges from 44.4% of the birth centers in MC to 87.5% in WE; and, finally, the ethical issues around the minimal GA limit to provide full resuscitation, ranging from 22 to 25 weeks across Europe. A comparison between high- and low-volume units showed significant differences in the domains of UC management and ventilation practices.    Conclusion: Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs. What is Known: • Delivery room (DR) support of preterm infants has a direct influence on both immediate survival and long-term morbidity. • Resuscitation practices for preterm infants often deviate from the internationally defined algorithms. What is New: • Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. • Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs.

Hospital-acquired skin lesions in the neonatal intensive care unit: A retrospective analysis of temporal trends and quality improvement strategies.

PURPOSE: Skin lesions in neonatal population are an emerging problem deserving attention from health care professionals. The purpose of this study is to retrospectively assess the incidence of hospital-acquired skin lesions during a 6-year period and to describe the characteristics of infants who developed them. DESIGN AND METHODS: This was a retrospective observational study conducted in a university-tertiary care center between 2015 and 2020. A descriptive analysis of the observed skin lesions is presented according to 2 time periods: 1) the implementation phase of a quality improvement program (2015-2019) and 2) the postimplementation phase (2020). RESULTS: Our findings showed an apparent increase in the incidence of all reported skin lesions throughout the study period. Pressure injuries were the most frequently reported skin lesions showing an increasing incidence over time which, however, was paralleled by a reduction in their severity. Among pressure injuries, device-related injuries were the most commonly observed (56.6% and 62.5% in the two periods, respectively) with nasal continuous positive airway pressure-related injuries accounting for 71.7% and 56.0% of lesions, respectively, and mainly affecting the nose root. The occipital area was the most frequently involved site in cases of conventional pressure injuries. CONCLUSION: Infants admitted to Neonatal Intensive Care Units may be at high risk of developing skin lesions. The adoption of appropriate preventative as well as treatment interventions could be effective in reducing the severity of pressure injuries. PRACTICE IMPLICATIONS: The implementation of quality improvement strategies may contribute to prevent skin injuries or lead to their early detection.

CXCR5-CXCL13 axis markers in full-term and preterm human neonates in the first weeks of life.

Term and preterm neonates have very few circulating Tfh-like cells (cTfh), and no circulating Tfr-like cells. Neonatal cTfh are CXCR5lo PD-1lo CD45RAhi , suggestive of a naive, possibly recently activated phenotype. CXCL13 is high at birth, but decreases rapidly in the first weeks of life. Overall, signs of GC activity in human neonates are weak, even in those born prematurely or after sepsis.

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.

Assessment of pregnancy dietary intake and association with maternal and neonatal outcomes.

BACKGROUND: Maternal dietary habits are contributors of maternal and fetal health; however, available data are heterogeneous and not conclusive. METHODS: Nutrient intake during pregnancy was assessed in 503 women with uncomplicated pregnancies, using the validated Food Frequency Questionnaire developed by the European Prospective Investigation into Cancer and Nutrition (EPIC-FFQ). RESULTS: In all, 68% of women had a normal body mass index at the beginning of pregnancy, and 83% of newborns had an appropriate weight for gestational age. Maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated with birth weight. GWG was not related to the pre-pregnancy BMI. EPIC-FFQ evaluation showed that 30% of women adhered to the European Food Safety Authority (EFSA) ranges for macronutrient intake. In most pregnant women (98.1%), consumption of water was below recommendations. Comparing women with intakes within EFSA ranges for macronutrients with those who did not, no differences were found in BMI, GWG, and neonatal or placental weight. Neither maternal nor neonatal parameters were associated with the maternal dietary profiles. CONCLUSIONS: In our population, maternal pre-pregnancy BMI, GWG, and placental weight are determinants of birth weight percentile, while no association was found with maternal nutrition. Future studies should explore associations through all infancy. IMPACT: Maternal anthropometrics and nutrition status may affect offspring birth weight. In 503 healthy women, maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated to neonatal birth weight. GWG was not related to the pre-pregnancy BMI. In all, 30% of women respected the EFSA ranges for macronutrients. Neither maternal nor neonatal parameters were associated with maternal dietary profiles considered in this study. Maternal pre-pregnancy BMI, GWG, and placental weight are determinants of neonatal birth weight percentile, while a connection with maternal nutrition profiles was not found.

SARS-CoV-2 infection and neonates: Evidence-based data after 18 months of the pandemic.

After 18 months of the COVID-19 pandemic, data concerning SARS-CoV-2 infection in pregnant women and their neonates are progressively taking the place of complete uncertainty. Here, we summarize updated evidence regarding several critical aspects of perinatal SARS-CoV-2 infection, including 1) vertical transmission of the virus in utero, which is possible but seems rare according to current epidemiological data; 2) how COVID-19 during pregnancy can shape maternal and neonatal outcomes, either directly or indirectly; 3) how recommendations regarding the management of infected dyads have been progressively modified in light of new scientific evidence; and 4) how maternal infection or vaccination can induce the passive protection of fetuses and neonates against the infection, through the transfer of specific antibodies before and after birth.

The care of critically ill infants and toddlers in neonatal intensive care units across Italy and Europe: our proposal for healthcare organization.

Numerous studies have shown that critically ill infants and toddlers admitted to paediatric intensive care units (PICUs) have a lower mortality than those admitted to adult ICUs. In 2014, there were only 23 registered PICUs in Italy, most of which were located in the north. For this reason, in Italy and elsewhere in Europe, some neonatal ICUs (NICUs) have begun managing critically ill infants and toddlers. Our proposal for healthcare organization is to establish "extended NICUs" in areas where paediatric intensive care beds are lacking. While some countries have opted for a strict division between neonatal and paediatric intensive care units, the model of "extended NICUs" has already been set up in Italy and in Europe. In this instance, the management of critically ill infants and toddlers undoubtedly falls upon neonatologists, who, however, must gain specific knowledge and technical skills in paediatric critical care medicine (PCCM). Postgraduate residencies in paediatrics need to include periods of specific training in neonatology and PCCM. The Italian Society of Neonatology's Early Childhood Intensive Care Study Group is supporting certified training courses for its members involving both theory and practice. CONCLUSION: Scientific societies should promote awareness of the issues involved in the intensive management of infants and toddlers in NICUs and the training of all health workers involved. These societies include the Italian Society of Neonatology, the European Society of Paediatric and Neonatal Intensive Care, and the Union of European Neonatal and Perinatal Societies. They should also act in concert with the governmental institutional bodies to establish the standards for the "extended NICUs." WHAT IS KNOWN: • The mortality of critically ill infants and toddlers admitted to PICUs is lower than that for those admitted to adult ICUs. • In Italy, there are only a handful of PICUs, located mainly in the north. WHAT IS NEW: • Critically ill infants and small toddlers can be managed in "extended NICUs" in areas with a lack of paediatric intensive care beds. • "Extended NICUs" is our proposal for healthcare organization to compensate for the paucity of paediatric intensive care beds, but neonatologists must be trained to provide them with specific knowledge and technical skills in PCCM.