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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 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.

Short bowel syndrome is the most common cause of intestinal failure (IF) in infants. We aimed to evaluate growth, nutrition intakes, and predictors of weaning from parenteral nutrition (PN) of infants with IF.Clinical parameters, nutrition intakes, body weight and length z-scores were compared monthly from the 1st to 12th and at 18 and 24 months among infants receiving PN and those weaned. Logistic regression analysis was conducted to explore the predictors of weaning.We included 23 infants (10/23 weaned). Median [range: minimum; maximum] birth weight and gestational age were 1620 [590; 3490] g and 31 [24; 39] weeks, respectively. All infants showed growth retardation with similar median delta weight z-score from birth to discharge: -1.48 [-1.92; -0.94] in not-weaned and -1.18 [-2.70; 0.31] in weaned infants (P = 0.833) and a subsequent regain after the discharge: 0.20 [-3.47; 3.25] and 0.84 [-0.03; 2.58], respectively (P = 0.518). No differences in length z-score were found. After the sixth month, infants weaned from PN received lower PN energy and protein intakes compared with those not-weaned. Infants weaned from PN showed lower PN dependency index (PNDI%) from 5 months onward (45% for weaned and 113% for not-weaned infants at 5 months: P 0.001). The Belza score, a predictor of enteral autonomy computed at 6 months, is associated with being weaned from PN within 24 months (odds ratio: 1.906; P = 0.039).Infants weaned and not-weaned showed similar growth patterns. Our findings support the clinical relevance of Belza score and PNDI% as predictors of weaning from PN.

In recent years, magnetic resonance imaging (MRI) has largely increased our knowledge and predictive accuracy of congenital diaphragmatic hernia (CDH) in the fetus. Thanks to its technical advantages, better anatomical definition, and superiority in fetal lung volume estimation, fetal MRI has been demonstrated to be superior to 2D and 3D ultrasound alone in CDH diagnosis and outcome prediction. This is of crucial importance for prenatal counseling, risk stratification, and decision-making approach. Furthermore, several quantitative and qualitative parameters can be evaluated simultaneously, which have been associated with survival, postnatal course severity, and long-term morbidity.Conclusion: Fetal MRI will further strengthen its role in the near future, but it is necessary to reach a consensus on indications, methodology, and data interpretation. In addition, it is required data integration from different imaging modalities and clinical courses, especially for predicting postnatal pulmonary hypertension. This would lead to a comprehensive prognostic assessment. What is Known:• MRI plays a key role in evaluating the fetal lung in patients with CDH.• Prognostic assessment of CDH is challenging, and advanced imaging is crucial for a complete prenatal assessment and counseling. What is New:• Fetal MRI has strengthened its role over ultrasound due to its technical advantages, better anatomical definition, superior fetal lung volume estimation, and outcome prediction.• Imaging and clinical data integration is the most desirable strategy and may provide new MRI applications and future research opportunities.

Breastmilk protects newborns from infections through specific and nonspecific compounds. This study investigated the neutralizing activity against SARS-CoV-2 of breastmilk from SARS-CoV-2 negative, unvaccinated mothers, and compared it to that from infected nursing mothers. We enrolled women after COVID-19 swab testing results upon maternity admission, and divided them into two groups: group A, COVID-19-positive mothers, and group B, negative mothers. Breastmilk was randomly sampled at 2, 7, and 20 days postpartum. We collected 19 samples for Group A and 41 for Group B. A microneutralization assay was used to determine the 50% neutralization (NT50) titre. The presence of neutralizing antibodies was also determined. Group A had 100% neutralizing samples at T0, declining in T1 and T2. Group B samples exhibited neutralizing activity mostly at T1 (90%). Negative mothers' samples showed no correlation between NT50 titres and antibodies' presence, suggesting that non-specific breast milk components may exert antiviral action against SARS-CoV-2.

Background: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking.Methods: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, Results: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups.Conclusions: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.). Background The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. Methods In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3–6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.

In a prospective cohort study of 65 inborn infants who were evaluated for late-onset sepsis at72 hours of age in 2 academic neonatal intensive care units, none had parechovirus or enterovirus RNA detected by polymerase chain reaction performed on nasopharyngeal specimens during the first or subsequent sepsis evaluations (n = 80).

To assess whether either duration and magnitude of ductal shunt or medical treatment for patent ductus arteriosus (PDA) are related to spontaneous intestinal perforation (SIP).Clinical charts of infants29 weeks' gestation born from 2006 to 2018 were reviewed. Echocardiographic examinations were evaluated according to McNamara and Sehgal's staging system.A higher percentage of patients with SIP had a hemodynamically significant PDA (HSPDA) and was treated with either NSAIDs or paracetamol (79% vs 53% and 81% vs 54%, respectively). Among non-treated patients, we found a 1.32 increase in the odds of SIP per day of persistence of HSPDA. In the cohort of patients treated despite the absence of HSPDA, we found a 2.35 increase in the odds of SIP per dose of drug administered.Both treating a non-HSPDA and leaving a HSPDA to its natural history seem to be associated with SIP.

Fresh frozen plasma (FFP) is largely misused in the neonatal setting. The aim of the study is to evaluate the impact of a Thromboelastography (TEG)-based Quality Improvement (QI) project on perioperative FFP use and neonatal outcomes. Retrospective pre-post implementation study in a level-III NICU including all neonates undergoing major non-cardiac surgery before (01–12/2017) and after (01–12/2019) the intervention. In 2018, the intervention included the following: (1) Training on TEG, (2) Implementation of TEG, and (3) Algorithm for TEG-directed FFP administration in surgical neonates. We compared pre- vs post-intervention patient characteristics, hemostasis, and clinical management. Linear and logistic regression models were used to evaluate the impact of the project on main outcomes. We analyzed 139 neonates (pre-intervention: 72/post-intervention: 67) with a mean (± SD) gestational age (GA) 34.9 (± 5) weeks and birthweight 2265 (± 980) grams which were exposed to 184 surgical procedures (pre-intervention: 91/post-intervention: 93). Baseline characteristics were similar between periods. In 2019, prothrombin time (PT) was longer (14.3 vs 13.2 s; p p p CI: 0.070, 0.371). Conclusion: The TEG-based QI project for the management of FFP during neonatal surgery reduced intraoperative FFP exposure. What is Known:• PT and aPTT are poor predictors of bleeding risk in acquired neonatal coagulopathy, leading to likely unnecessary fresh frozen plasma (FFP) transfusion in the Neonatal Intensive Care Setting. • As neonatal hemostasis is a delicate balance between the concomitant reduction of pro- and anti-coagulants drivers, thromboelastography (TEG) is a promising alternative for coagulation monitoring. What is New:• The implementation of TEG, training, and shared protocols contributed to reduced intraoperative FFP use, which was not associated with increased mortality or bleeding events.• These findings inform future research showing that there is clinical equipoise to allow for larger studies to confirm the use of TEG in NICUs and to identify TEG cut-offs for transfusion practice.

Although traditionally considered sterile, human milk is currently recognized as an alive ecosystem that harbors not only bacteria, but also viruses, fungi and yeasts, and minor genera, collectively known as the human milk microbiome (HMM). The seeding of HMM is a complex phenomenon whose dynamics are still a matter of research. Many factors contribute to its determination, both maternal, neonatal, environmental, and related to human milk itself. The transmission of microorganisms to the infant through breastfeeding may impact its present and future health, mainly shaping the GI tract microbiome and immune system. The existence and persistence of HMM as a conserved feature among different species may also have an evolutionary meaning, which will become apparent only in evolutionary times.Conclusion: The complexities of HMM warrant further research in order to deepen our knowledge on its origin, determinants, and impact on infants’ health. The practical and translational implications of research on HMM (e.g., reconstitution of donor human milk through inoculation of infant’s own mother milk, modulation of HMM through maternal dietary supplementation) should not be overlooked. What is Known:• Human milk harbors a wide variety of microorganisms, ranging from bacteria to viruses, fungi and yeasts, and minor genera.• Human milk microbiome is shaped over time by many factors: maternal, neonatal, environmental, and related to human milk itself.• The transmission of microorganisms through breastfeeding may impact the infant’s present and future health. What is New:• We provide an overview on human milk microbiome, hopefully encouraging physicians to consider it among the other better-known breastfeeding benefits.• Further studies, with standardized and rigorous study designs to enhance accuracy and reproducibility of the results, are needed to deepen our knowledge of the human milk microbiota and its role in newborn and infant’s health.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

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.

Background Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome. Research Question Can LUS also predict the need for surfactant replacement? Study Design and Methods Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to F io 2 ratio, F io 2, and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to F io 2 ratio for surfactant administration, adjusting for gestational age (GA), were analyzed through a logistic regression model. Results Two hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks’ GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks’ GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks’ GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing F io 2, oxygen saturation to F io 2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to F io 2 ratio and LUS showed the highest predictive power, with an AUC of 0.93 (95% CI, 0.89-0.97), regardless of the GA interval. Interpretation LUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to F io 2 ratio significantly improves the prediction power for surfactant need.

BackgroundHuman milk is a vehicle for bioactive compounds and beneficial bacteria which promote the establishment of a healthy gut microbiome of newborns, especially of preterm infants. Pasteurized donor human milk (PDHM) is the second-best option when preterm mother’s own milk is unavailable. Since pasteurization affect the microbiological quality of donor milk, PDHM was inoculated with different preterm milk samples and then incubated, in order to evaluate the effect in terms of bacterial growth, human milk microbiome and proteolytic phenomena.MethodsIn an in-vitro study PDHM was inoculated at 10% v/v using ten preterm milk samples. Microbiological, metataxonomic and peptidomic analyses, on preterm milk samples at the baseline (T0), on PDHM and on inoculated milk (IM) samples at T0, after 2 h (T1) and 4 h (T2) of incubation at 37 °C, were conducted.ResultsIM samples at T2 showed a Total Bacterial Count not significantly different (p > 0.01) compared to preterm milk samples. At T2 lactic acid bacteria level was restored in all IM. After inoculation, metataxonomic analysis in IM samples showed that Proteobacteria remained the predominant phylum while Firmicutes moved from 3% at T1 to 9.4% at T2. Peptidomic profile of IM resembled that of PDHM, incubated for the same time, in terms of number and type of peptides.ConclusionThe study demonstrated that inoculation of PDHM with mother’s own milk could restore bacterial growth and personalize human milk microbiome in PDHM. This effect could be beneficial because of the presence of maternal probiotic bacteria which make PDHM more similar to mother’s own milk.

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants’ clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high.

Objectives and Study: Docosahexaenoic acid (DHA) plays an essential role in infants’ development. Maternal diet and breastmilk are the primary DHA sources for newborns. This single-center observational study aimed to compare the DHA content in mother’s milk of preterm mothers with that of term ones, and to investigate the changes in mother’s milk DHA content according to the week of the gestational age. Methods: A food frequency questionnaire (FFQ) was submitted to each mother to estimate the DHA intake during the last trimester of pregnancy, and the mother’s milk was collected between 24 and 96 h post-partum. Results: Women who gave birth prematurely showed a lower content of mother’s milk DHA than the term ones (0.51; IQR 0.38–0.6% FA vs. 0.71; IQR 0.52–0.95% FA; p = 0.001). In the multivariate linear regression analyses, for each additional week of gestational age, there was an increase in DHA content in the mother’s milk (0.046% FA; CI 95% 0.018–0.074; p < 0.001). Conclusions: Our results suggest that breast milk may not be sufficient to fully satisfy the recommended DHA intake in preterm infants. This study may represent a starting point to investigate new possible DHA supplementation strategies, especially for the late and moderate preterm infants.

To evaluate the impact of human milk and different neonatal variables on tidal breathing flow-volume loop (TBFVL) parameters within three months' corrected age (CA) in infants born ≤32 wks or weighing1500 g.We retrospectively studied 121 infants with gestational age (GA) ≤ 32 weeks or birth weight (BW) 1500 gr who had lung function assessment within three months' CA by TBFVL analysis between June 2009 and April 2018. We investigated the impact of GA, gender, being Small for GA (SGA), sepsis, days of mechanical ventilation (MV) and human milk feeding (HMF) on later respiratory function, both in the entire group and according to BW ( ≤1000 g and1000 g).The mean(SD) z-score for tidal volume (Vt) and time to peak expiratory flow to expiratory time (tPTEF/tE) were respectively -4.3 (2.5) and -0.8 (2.0) for the overall population with no significant differences between infants1000 g or ≥1000 g. The mean(SD) Vt standardized for body weight was 6.2(2.0) ml/kg. Being female was associated with better Vt/Kg, whereas longer MV or being born SGA were associated with worst tPTEF/tE. For infants with BW 1000 gr, tPTEF/tE was positively associated with HMF.An early TBFVL assessment within three months' CA already reveals lung function alteration in preterm infants. Being female is associated with better Vt/Kg, while longer duration of MV or being born SGA negatively affect tPTEF/tE. The positive association between HMF and better tPTEF/tE in infants with BW1000 g has emerged, which deserves further investigation.

In newborns with congenital diaphragmatic hernia (CDH), the mediastinal shift caused by the herniated organs negatively affects lung development. Assessment of the fetal magnetic resonance imaging (MRI) mediastinal shift angle (MSA) was shown to have an inverse correlation with the total fetal lung volume (TFLV), being associated with neonatal survival. However, a possible association with postnatal morbidity has never been investigated. We hypothesize that the degree of the mediastinal shift could be associated with higher respiratory and cardiocirculatory impairment, requiring intensive treatments and extended hospitalization in survivors. We retrospectively consider a cohort of isolated, left-sided CDH, for whom we calculated the MSA and the observed/expected (O/E) TFLV at fetal MRI. We performed a data collection regarding inotropic or vasoactive support, treatment with pulmonary vasodilators, mechanical ventilation, and length of stay. General linear models were performed. The MSA and O/E TFLV were inversely correlated (Pearson’s coefficient − 0.65, p < 0.001), and deceased patients showed higher MSA values then survivors (p = 0.011). Among survivors, an increase in MSA was associated with longer pharmacological treatments (dobutamine: p = 0.016; dopamine: p = 0.049; hydrocortisone: p = 0.003; nitric oxide: p = 0.002; sildenafil: p = 0.039; milrinone: p = 0.039; oxygen: p = 0.066), and mechanical ventilation (p = 0.005), with an increasing trend in the length of hospitalization (p = 0.089). Conclusion: The MSA indirectly reflects lung hypoplasia and is associated with a higher neonatal intensity of cares. However, further studies are needed to consolidate the results. Trial registration: The study is an exploratory post hoc analysis of the registered NeoAPACHE protocol at ClinicalTrials.gov with the identifier NCT04396028.

The present article shows the current neonatal air transport organization and activity in Italy. The results were obtained on the basis of a recent 2019 survey (year of activity 2018) performed by the Neonatal Transport Study Group of the Italian Society of Neonatology. The total number of newborn transports during the year 2018 was 6,464. The air-suitable transports were 512 of 5,852 (8.74%), and among them, 101 of 512 (19.72%) were performed by helicopter and 34 by airplane. Besides the availability of air transport, the interfacility distance, weather and traffic conditions, and rural mountainous roads were the main factors in determining the vehicle choice. Neonatal air transport in Italy is not homogeneously distributed and needs organizational corrections. The high density of neonatal emergency transport services on the national territory indicates the need to overcome the limits imposed by regional administrative borders, thus expanding the geographic area of competence.

Rationale: Lung ultrasound is useful in critically ill patients with acute respiratory failure. Given its characteristics, it could also be useful in extremely preterm infants with evolving chronic respiratory failure, as we lack accurate imaging tools to monitor them. Objectives: To verify if lung ultrasound can monitor lung aeration and function and has good reliability to predict bronchopulmonary dysplasia in extremely preterm neonates. Methods: A multicenter, international, prospective, longitudinal, cohort, diagnostic accuracy study consecutively enrolling inborn neonates with gestational age 3016 weeks or younger. Lung ultrasound was performed on the 1, 7, 14, and 28 days of life, and lung ultrasound scores were calculated and correlated with simultaneous blood gases and work of breathing score. Gestational age-adjusted lung ultrasound scores were created, verified in multivariate models, and subjected to receiver operator characteristics (ROC) analyses to predict bronchopulmonary dysplasia at 36 weeks postmenstrual age. Measurements and Main Results: Mean lung ultrasound scores are different between infants developing (n572) or not developing (n575) bronchopulmonary dysplasia (P,0.001 at any time point). Lung ultrasound scores significantly correlate with oxygenation metrics and work of breathing at any time point (P always,0.0001). Gestational age-adjusted lung ultrasound scores significantly predict bronchopulmonary dysplasia at 7 (area under ROC curve, 0.826-0.833; P,0.0001) and 14 (area under ROC curve, 0.834-0.858; P,0.0001) days of life. Bronchopulmonary dysplasia severity and gestational age-adjusted lung ultrasound scores are significantly correlated at 7 and 14 days (P always,0.0001). Conclusions: Lung ultrasound scores allow monitoring of lung aeration and function in extremely preterm infants. Gestational age-adjusted scores significantly predict the occurrence of bronchopulmonary dysplasia, starting from the seventh day of life.

Extracorporeal membrane oxygenation (ECMO) is a life-saving support for cardio-respiratory function. Over the last 50 years, the extracorporeal field has faced huge technological progress. However, despite the improvements in technique and materials, coagulation problems are still the main contributor to morbidity and mortality of ECMO patients. Indeed, the incidence and survival rates of the main hemorrhagic and thrombotic complications in neonatal respiratory ECMO are relevant. The main culprit is related to the intrinsic nature of ECMO: the contact phase activation. The exposure of the human blood to the non-endothelial surface triggers a systemic inflammatory response syndrome, which chronically activates the thrombin generation and ultimately leads to coagulative derangements. Pre-existing illness-related hemostatic dysfunction and the peculiarity of the neonatal clotting balance further complicate the picture. Systemic anticoagulation is the management's mainstay, aiming to prevent thrombosis within the circuit and bleeding complications in the patient. Although other agents (i.e., direct thrombin inhibitors) have been recently introduced, unfractionated heparin (UFH) is the standard of care worldwide. Currently, there are multiple tests exploring ECMO-induced coagulopathy. A combination of the parameters mentioned above and the evaluation of the patient's underlying clinical context should be used to provide a goal-directed antithrombotic strategy. However, the ideal algorithm for monitoring anticoagulation is currently unknown, resulting in a large inter-institutional diagnostic variability. In this review, we face the features of the available monitoring tests and approaches, mainly focusing on the role of point-of-care (POC) viscoelastic assays in neonatal ECMO. Current gaps in knowledge and areas that warrant further study will also be addressed.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving support for respiratory and cardiovascular failure. However, ECMO induces a systemic inflammatory response syndrome that can lead to various complications, including endothelial dysfunction in the cerebral circulation. We aimed to investigate whether ECMO-associated endothelial dysfunction also affected coronary circulation. Ten-day-old piglets were randomized to undergo either 8 h of veno-arterial ECMO (n = 5) or no treatment (Control, n = 5). Hearts were harvested and coronary arteries were dissected and mounted as 3 mm rings in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U46619, concentration–response curves to the endothelium-dependent vasodilator bradykinin (BK) and the nitric oxide (NO) donor (endothelium-independent vasodilator) sodium nitroprusside (SNP) were performed. Relaxation to BK was studied in the absence or presence of the NO synthase inhibitor Nω-nitro-L-arginine methyl ester HCl (L-NAME). U46619-induced contraction and SNP-induced relaxation were similar in control and ECMO coronary arteries. However, BK-induced relaxation was significantly impaired in the ECMO group (30.4 ± 2.2% vs. 59.2 ± 2.1%; p < 0.0001). When L-NAME was present, no differences in BK-mediated relaxation were observed between the control and ECMO groups. Taken together, our data suggest that ECMO exposure impairs endothelium-derived NO-mediated coronary relaxation. However, there is a NO-independent component in BK-induced relaxation that remains unaffected by ECMO. In addition, the smooth muscle cell response to exogenous NO is not altered by ECMO exposure.

Background CHARGE syndrome (CS) is an autosomal dominant genetic condition whose recognition in the neonatal period is complicated by considerable phenotypic variability. Pediatric patients with genetic disorders have a known high incidence of hypoglycemia, due to many concurring factors. To date, neonatal hypoglycemia is a feature poorly explored in the literature associated with CS. This paper adds to the existing literature on hypoglycemia in CS and provides a brief review of the mechanisms through which CS, as well as the main genetic syndromes associated with neonatal hypoglycemia, may determine it. Case presentation The patient was a term newborn, first-born daughter to non-consanguineous parents. At birth, axial hypotonia with slight hypertonia of the limbs, and dysplastic auricles were noted. The incidental finding of asymptomatic hypoglycemia led to the initiation of glucose infusion on the II day of life, continued for a total of 8 days (maximum infusion rate: 8 mg/kg/min). In-depth endocrinological examinations showed poor cortisol response to the hypoglycemic stimulus, with normal GH values, thyroid function and ACTH. In view of the suspected hypoadrenalism, oral hydrocortisone therapy was initiated. Inappropriately low values of plasmatic and urinary ketones supported the hypothesis of concomitant transient hyperinsulinism, not requiring therapy. A brain MRI was performed, documenting thinning of the optic nerves, non-displayable olfactory bulbs and dysmorphic corpus callosum. An eye examination revealed bilateral chorioretinal coloboma. Temporal bone CT scan showed absence of the semicircular canals. The unexpected findings of coloboma and absence of semicircular canals led to the suspicion of CS, later confirmed by the molecular analysis of CHD7. Conclusions It seems important to consider CS in the differential diagnosis of persistent hypoglycemia in newborns with specific anomalies. At the same time, it is advisable to consider the risk of hypoglycemia in children with CS, as well as other genetic syndromes. Awareness of the many possible causes of hypoglycemia in newborns with genetic conditions may help steer the investigations, allowing for an appropriate and timely treatment.

Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16–23% in very-low-birth-weight (VLBW, birth weight

The magnitude of mother-to-infant transfer of anti-SARS-CoV-2 antibodies through breast milk (BM) after maternal vaccination during breastfeeding, in the absence of transplacental transfer of IgG, remains unclear. Here, we quantified anti-S and anti-RBD IgG, IgA, IgA1, and IgA2 in maternal serum, maternal saliva, BM, infant buccal swabs, and infant feces up to 90 days after the second maternal vaccine dose. BNT162b2 vaccine induced long-lasting IgG in maternal serum, but weaker mucosal antibody production, with anti-SARS-CoV-2 IgG and IgA amounts in BM between 10- and 150-fold lower compared to serum. BM IgA were exclusively of the IgA1 isotype, with no production of the mucosal-specific and protease-resistant IgA2. Accordingly, only traces of antibodies were retrieved from the feces of breastfed infants, and no IgG nor IgA were retrieved from infants’ buccal swabs. Newly engineered anti-SARS-CoV-2 vaccines may be needed to stimulate the antibody production at mucosal sites such as breast milk.

A reduced nephron number may play a role in the pathogenesis of arterial hypertension (AH), and it is well recognized that individual nephron endowment is widely variable. However, nephrons count is technically impossible in vivo. Based on the observation that subjects with a reduced nephron mass exhibit an increase in renal functional biomarkers during acute dehydration, we hypothesized that cystatin C concentration during neonatal physiological dehydration could identify subjects with reduced nephron endowment. This is a prospective, observational, cohort study enrolling healthy, caucasian, term neonates born after an uneventful pregnancy. Two groups of newborns were compared: neonates born to fathers on antihypertensive treatment (HF) versus those born to proven normotensive fathers older than 40 years of age (NF). Enrolled newborns underwent cystatin C determination at the time of newborn screening. Forty newborns with HF and 80 with NF were enrolled. No differences in baseline characteristics were observed between the two groups except for the number of hypertensive grandparents higher among newborns to HF (47.8% vs. 21.1%; p: 0.001). Cystatin C was significantly higher in newborns with HF (1.62 ± 0.30 mg/L vs 1.41 ± 0.27 mg/L; p

OBJECTIVE To derive testing and treatment thresholds for early-onset neonatal sepsis and compare them to thresholds used in the Kaiser-Permanente (KP) Sepsis Calculator. METHODS Using surveys distributed in the United States, Brazil and Italy, decision thresholds were derived via self-identified thresholds selected from structured lists (Method 1), and based on clinical vignette responses for testing and treatment with or without inclusion of associated relative risk (Methods 2 and 3). RESULTS Using Method 1, both testing and treatment thresholds were higher than the KP calculator thresholds. Test thresholds were lower (Method 2) or equivalent (Method 3) to KP using clinical vignettes. No vignette reached the 50% cutoff necessary to define a treatment threshold. CONCLUSION The test threshold used by the KP calculator is the same as the threshold chosen by clinicians given a vignette and risk estimate. The KP treatment threshold is lower than that derived using all 3 methods.

Late preterm infants constitute the largest subset of premature infants and are more likely to experience feeding issues leading to delayed oral feeding independence and low breastfeeding rates. Considering the increased parental concern about their infants’ nutrition and growth, we performed a literature review to provide an update on the feeding challenges faced by late preterm infants and the impact of these issues on maternal mental health and the mother–infant relationship. Based on our findings, late preterm infants have a high prevalence of feeding difficulties which need to be addressed by targeted support interventions to promote breastfeeding success and the establishment of a harmonious dyadic interaction between the mother and her infant, all of which contribute to the prevention of altered feeding behavior later in life. There is still a need for additional research to develop a standardized and shared strategy that can be proven to be effective. Should this be accomplished, it will be possible to offer appropriate support for mothers, encourage the oral skills and maturation of late preterm infants, and improve the relationship quality within the dyad.

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. Term and preterm neonates have very few circulating Tfh-like cells (cTfh), and no circulating Tfr-like cells. Neonatal cTfh are CXCR5(lo)PD-1(lo)CD45RA(hi), 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. (dagger)

Neonatal extracorporeal membrane oxygenation (ECMO) is a life-saving procedure for critically ill neonates suffering from a potentially reversible disease, causing severe cardiac and/or respiratory failure and refractory to maximal conventional management. Since the 1970s, technology, management, and clinical applications of neonatal ECMO have changed. Pulmonary diseases still represent the principal neonatal diagnosis, with an overall 74% survival rate, and up to one-third of cases are due to congenital diaphragmatic hernia. The overall survival rate in cardiac ECMO is lower, with congenital heart defect representing the main indication. This review provides an overview of the available evidence in the field of neonatal ECMO. We will address the changing epidemiology, basic principles, technologic advances in circuitry, and monitoring, and deliver a current multidisciplinary management framework, focusing on ECMO applications, complications, and long-term morbidities. Lastly, areas for further research will be highlighted.Conclusions: ECMO is a life support with a potential impact on long-term patients' outcomes. In the next years, advances in knowledge, technology, and expertise may push neonatal ECMO boundaries towards more premature and increasingly complex infants, with the final aim to reduce the burden of ECMO-related complications and improve overall patients' outcomes. What is Known: • ECMO is a life-saving option in newborns with refractory respiratory and/or cardiac failure. • The multidisciplinary ECMO management is challenging and may expose neonates to complications with an impact on long-term outcomes. What is New: • Advances in technology and biomaterials will improve neonatal ECMO management and, eventually, the long-term outcome of these complex patients. • Experimental models of artificial placenta and womb technology are under investigation and may provide clinical translation and future research opportunities.

Background Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, which may dysregulate platelet function. Total Thrombus-Formation Analysis System (T-TAS) is a flow-chamber device that analyses platelet-mediated thrombus formation in capillary channels through the following parameters: (1) the area under the flow-pressure curve (AUC), (2) occlusion start time (OST), time needed to reach OST, and (3) occlusion time (OT), time needed to reach the occlusion pressure. Methods and Findings Sixty-one COVID-19 patients admitted to intensive, subintensive, and low intensive care were prospectively enrolled according to the time of admission: group A (up to 8 days) (n = 18); group B (from 9 to 21 days) (n = 19), and group C ( > 21 days) (n = 24). T-TAS measurements were performed at enrolment and after 7 days. Median OST was similar among groups. AUC was lower in group A compared to B (p = 0.001) and C (p = 0.033). OT was longer in group A compared to B (p = 0.001) and C (p = 0.028). Platelet count (PC) was higher in group B compared to A (p = 0.024). The linear regression showed that OT and AUC were independent from PC in group A (OT: 0.149 [95% confidence interval [CI]: –0.326 to 0.624], p = 0.513 and AUC: 0.005 [95% CI: –0.008 to 0.017], p = 0,447). In contrast, in group B, PC was associated with OT (–0.019 [–0.028 to 0.008], p = 0.023) and AUC (0.749 [0.358–1.139], p = 0,015), similarly to group C. Conversely, patients with different illness severity had similar T-TAS parameters. Conclusion COVID-19 patients display an impaired platelet thrombus formation in the early phase of the disease compared to later stages and controls, independently from illness severity.

Early in the Covid-19 pandemic maternity hospital practices were jeopardized by guidelines produced by scientific societies to reduce the risk of mother to child transmission of the SARS-CoV-2 infection to a minimum. Subsequent research has documented that skin-to-skin contact in the delivery room, feeding directly to the breast and rooming-in can be considered safe, if infection control measures are concurrently applied. Professionals should not forget the proven benefits of breastfeeding and the importance of early mother-baby relationship whenever taking decisions that might hinder these practices.

Very preterm infants are exposed to prenatal inflammatory processes and early postnatal hemodynamic and respiratory complications, but limited data are available about the endothelial effect of these conditions. The present pilot study investigates the perinatal endothelial phenotype in very preterm infants (VPIs) and explores its predictive value on neonatal mortality and hemodynamic and respiratory complications. Angiopoietin 1 (Ang-1), Ang-2, E-selectin, vascular adhesion molecule 1 (VCAM-1), tissue factor (TF), and endothelin 1 (ET-1) concentrations were tested in first (T1), 3rd (T2), and 7–10th (T3) day of life in 20 VPIs using Luminex technology and compared with 14 healthy full-term infants (FTIs). Compared to FTIs, VPIs had lower Ang-1 at T1 and T2; higher Ang-2 at T1, T2, and T3; higher Ang-2/Ang-1 ratio at T1, T2, and T3; lower E-selectin at T1, T2, and T3; higher VCAM-1 at T1; higher TF at T2. No differences in concentrations were found in neonatal deaths. VPIs with hemodynamic or respiratory complications had higher Ang-2 at T3. Perinatal low Ang-1 and high Ang-2 associated with high VCAM-1 and TF in VPIs suggest a proinflammatory endothelial phenotype, resulting from the synergy of a pathological prenatal inheritance and a premature extrauterine transition.

Infants born preterm are at high risk of presenting neurodevelopmental delay. The Neurofunctional Assessment (NFA) describes infants’ neurodevelopment through the evaluation of six different domains. This study aimed to evaluate how, in a cohort of preterm infants, each NFA domain assessed at 3 months of corrected age (CA) was associated with neurodevelopment at 2 years of CA using the Griffiths Mental Developmental Scales Extended Revised (GMDS-ER). In addition, by introducing the NFA complexity score (CS), the study aimed to define a threshold that can help clinicians discriminate infants at higher risk of later neurodevelopmental delay. We conducted an observational, longitudinal study including 211 preterm infants. At 3 months of CA, infants who had normal scores in each domain showed a significantly higher GMDS-ER global quotient (GQ) at 2 years of CA. In addition, linear model results showed a significant negative relationship between the NFA CS and 2-year GMDS-ER GQ (estimate: − 0.27; 95% CI − 0.35, − 0.20; p value

Pediatric neurosurgery is a highly specialized branch of surgery in which surgical site infections (SSIs) are potentially serious complications that can also adversely affect a good surgical outcome, compromising functional recovery and, in some cases, even putting the patient’s life at risk. The main aim of this consensus document is to provide clinicians with a series of recommendations on antimicrobial prophylaxis for neonates and children undergoing neurosurgery. The following scenarios were considered: (1) craniotomy or cranial/cranio-facial approach to craniosynostosis; (2) neurosurgery with a trans-nasal-trans-sphenoidal approach; (3) non-penetrating head injuries; (4) penetrating head fracture; (5) spinal surgery (extradural and intradural); (6) shunt surgery or neuroendoscopy; (7) neuroendovascular procedures. Patients undergoing neurosurgery often undergo peri-operative antibiotic prophylaxis, with different schedules, not always supported by scientific evidence. This consensus provides clear and shared indications, based on the most updated literature. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, and represents, in our opinion, the most complete and up-to-date collection of recommendations on the behavior to be held in the peri-operative setting in this type of intervention, in order to guide physicians in the management of the patient, standardize approaches and avoid abuse and misuse of antibiotics.

In the late 2020s, less than 1 year into the coronavirus disease 2019 (COVID-19) pandemic, several anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines were introduced on a worldwide scale, with a significant positive impact on the consequences of the disease for several high-risk population groups. In the case of most bacterial or viral respiratory infections, pregnant women are at increased risk of complications, however, neither pregnant nor breastfeeding women were included in the first round of randomized clinical trials evaluating the safety and effectiveness of COVID-19 vaccines, because of safety and ethical concerns. Nevertheless, most anti-SARS-CoV-2 vaccines have not been expressly contraindicated during pregnancy or breastfeeding, and observational data on immune response, adverse effects, and clinical efficacy in pregnant and breastfeeding women have been progressively gathered during 2021. The vast majority of these data is reassuring for what concerns side effects for women and infants and points out the efficacy of vaccines in protecting women against COVID-19-related complications. Despite this, the hesitancy of pregnant and breastfeeding women at being vaccinated is still real. In this mini-review, we resume the available data on the clinical consequences of COVID-19 in pregnant women, as well as adverse effects, systemic and mucosal immune response, and clinical effectiveness of COVID-19 vaccines in pregnant and breastfeeding women. Moreover, we offer an updated overview of European, North American, and Australasian recommendations concerning COVID-19 vaccination in pregnant and breastfeeding women, in order to safely ensure the highest protection of women and their infants.

The Parent Health Locus of Control (PHLOC) investigates the individual's beliefs about the factors that govern their state of health and that of their children. The direct association between PHLOC and preventive health behaviours compliance has already been demonstrated in the literature. However, it is still unclear how socio-demographic variables affect the PHLOC. We investigated the Parent Health Locus of Control of parents of full-term and preterm infants and evaluated whether there were any correlations between PHLOC and socio-demographic characteristics of both parents and infants. A single-centre transverse observational study was conducted in the Neonatology Operating Unit IRCCS Ca 'Granda Foundation Ospedale Maggiore Policlinico of Milan. A self-administered questionnaire of the PHLOC scale was distributed to a sample of 370 parents of 320 full-term and 52 preterm infants attending the follow-up service. Parents under the age of 36 and with a higher level of education (bachelor's degree or above) believe less in the influence of the media on their child's health. Parents of preterm and first-child infants recognize the greater influence of health care workers, while parents of newborns that have experience complications in their clinical course, believe more in the influence of fate (Chance Health Locus of Control) and God. Younger parents with a higher level of education may be more prone to healthy preventative behaviours. Preterm birth is positively associated with an increased trust in health care professionals. The experience of disease can increase a "Chance Health Locus of Control" and risky behaviours. Assessment of PHLOC helps identify categories of parents prone to risky health behaviours and offer targeted health education interventions.

BackgroundViscoelastic coagulation tests provide valuable information in neonatal intensive care units (NICUs), but the lack of reference intervals still limits their decision-making power according to gestational age. The aim of the present study is to evaluate the hemostasis of a cohort of full-term (FT) and late-preterm (LP) infants using the viscoelastic coagulation monitor (VCM®) system, a new portable device that uses untreated whole blood.MethodsAn observational study was performed to identify non-coagulopathic FT and LP infants admitted to III° level NICU (January 2020 to December 2021) with a VCM test in the first 72 h of life.ResultsForty-five patients were enrolled, 26 FT and 19 LP. No statistical differences in hemostatic parameters were observed between FT and LP nor between stable and unstable neonates. Clotting time (CT) was positive correlated with PT (p = 0.032), not with aPTT (p = 0.185). From linear regression, platelet resulted associated with: clot formation time (CTF, p = 0.003), alpha angle (Alpha, p = 0.010), amplitude at 10 (A10, p = 0.001), amplitude at 20 min (A20, p < 0.001), maximum clot firmness (MCF, p < 0.001); and fibrinogen was associated with: A10 (p = 0.008), A20 (p = 0.015) and MCF (p = 0.024). Compared to the adult reference population, neonates showed shorter CT (mean (SD): 5.3 (1.4) vs. 7.0 (0.9) min, p < 0.001), CFT (2.4 (0.7) vs. 2.8 (0.6) minutes, p < 0.001) and higher Alpha (60.8 (6.3) vs. 55 (5)°, p < 0.001). In addition, the neonatal cohort showed an early transient difference in amplitude and fibrinolysis, as follows: A10 (28.0 (5.0) vs. 26 (4) VCM units, p =0.004), A20 (34.8 (5.0) vs. 33 (4) VCM units, p =0.012), and LI30 (99.8 (0.5) vs. 99 (1)%, p ConclusionsThe viscoelastic profile of FT and LP infants assessed with VCM showed a hemostatic competence characterized by accelerated coagulation and clot formation time, in line with other viscoelastic techniques. VCM system provides promising applications in the NICU setting.

In the context of SARS-CoV-2 pandemic, the hospital management of mother-infant pairs poses to obstetricians and neonatologists previously unmet challenges. In Lombardy, Northern Italy, 59 maternity wards networked to organise the medical assistance of mothers and neonates with suspected or confirmed SARS-CoV-2 infection. Six “COVID-19 maternity centres” were identified, the architecture and activity of obstetric and neonatal wards of each centre was reorganised, and common assistance protocols for the management of suspected and proven cases were formulated. Here, we present the key features of this reorganization effort, and our current management of the mother-infant dyad before and after birth, including our approach to rooming-in practice, breastfeeding and neonatal follow-up, based on the currently available scientific evidence. Considered the rapid diffusion of COVID-19 all over the world, we believe that preparedness is fundamental to assist mother-infant dyads, minimising the risk of propagation of the infection through maternity and neonatal wards.

Background and objectives Despite low incidence of early-onset sepsis, the majority of preterm newborns receive early antibiotic prophylaxis. Our aim was to assess reference ranges of Presepsin during the first 48 h of life in preterm infants and to evaluate the possible influence of neonatal and maternal factors on its values. Methods This observational study consecutively enrolled newborns ≤ 32 weeks of GA at 0–6 h of life. Enrolled infants were sampled for blood culture, complete white blood cell (WBC) count, and P-SEP at 0–6 (T0) h of life and for P-SEP at 12 ± 3 (T1), 24 ± 3 (T2), and 48 ± 6 (T3) h of life. Cases of EOS were not considered for the statistical analysis. Results Data analysis was performed for 183 patients. P-SEP median values were 583 ng/L at T0 (IQR 405–800 ng/L, 5th and 95th percentiles 204 and 1200 ng/L), 614 ng/L at T1 (IQR 450–812 ng/L, 5th and 95th percentiles 262 and 1171 ng/L), 604 ng/L at T2 (IQR 445–825 ng/L, 5th and 95th percentiles 292 and 1302 ng/L) and 513 ng/L at T3 (IQR 371–734 ng/L, 5th and 95th percentiles 249 and 1278 ng/L). P-SEP values are negatively associated to gestational age (GA) at T0, T1, and T2. Conclusions We determined for the first time the reference ranges of P-SEP during the first 48 h of life in very preterm infants and provided its percentile distribution at T0, T1, T2 and T3. P-SEP measurement was affected by GA at T0, T1, T2.

The aim of the study was to investigate General Movements’(GMs) neonatal trajectories and their association with neurodevelopment at three months corrected age (CA) in preterm infants. We conducted an observational, longitudinal study in 216 very low birth weight infants. GMs were recorded at 31 ± 1, 35 ± 1, 40 ± 1 weeks of postmenstrual age and at three months of corrected age (CA). More than 90% of infants showing neonatal trajectories with persistent Normal (N-N) or initial Poor Repertoire to Normal (PR-N) movements presented fidgety pattern at three months CA. On the contrary, fidgety movements were not detected in any infant with a trajectory of persistent Cramped-Synchronized (CS-CS) or an initial Poor-Repertoire to Cramped-Synchronized (PR-CS) movements. Trajectories with initial Normal to Poor-Repertoire (N-PR) or persistent Poor-Repertoire (PR-PR) movements showed an increased risk of having a non-normal Fidgety pattern compared with the N-N group (OR = 8.43, 95% CI: 2.26–31.45 and OR = 15.02, 95% CI: 6.40–35.26, respectively). These results highlight the importance to evaluate neonatal GMs’ trajectory to predict infants’ neurodevelopment. N-N or PR-N trajectories suggest normal short-term neurodevelopment, especially a lower risk of Cerebral Palsy; whereas findings of N-PR and PR-PR trajectories indicate the need for closer follow up to avoid delay in programming intervention strategies.

The benefits of human milk in preterm infants, a population at high risk for developing adverse outcomes for which breast milk is a protective factor, are widely acknowledged. However, preterms’ admission in a neonatal intensive care unit (NICU) and newborn’s clinical conditions have been described as significant barriers, leading to lower rates of breastfeeding initiation and duration. Healthcare workers play a crucial role in encouraging breastfeeding. We conducted a cross-sectional survey among nurses working in six Italian NICUs, exploring their knowledge and attitude towards breastfeeding. Although the majority of nurses had a specific breastfeeding education, our results show still some variations among answers regarding aspects of breastfeeding support in this setting. Specifically, family-centered care, transition feeding to the breast, and skin-to-skin practice, despite being extensively addressed by the Neo Baby-Friendly Hospital Initiative, are the items that highlighted a range of answers that could result in conflicting information to mothers. Conclusion: By underlining the gaps of knowledge and attitude towards breastfeeding of nurses working in NICUs, this study provides an insight into what needs to be improved, with the aim of promoting higher rates of breastfeeding in the preterm population.