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Background: Anakinra is an interleukin-1 receptor antagonist (IL-1Ra). Since IL-1 has been shown to play a key role in the etiology of different autoinflammatory diseases, blocking its pathway has become an important therapeutic target, even in neonates., Aims: We aimed to report our experience in using anakinra to treat specific neonatal inflammatory conditions., Methods: We described the clinical management with anakinra of five cases of neonates or infants up to 3 months of age admitted to the neonatal intensive care unit (NICU) of Bambino Gesù Children's Hospital IRCCS in Rome (Italy) from 2020 onwards. Medical history and clinical data concerning NICU hospitalization were collected from the electronic medical records. Furthermore, we performed a literature review of off-label anakinra in the first 3 months of life, up to 5 April 2024. We excluded from this review cases of cryopyrin-associated periodic syndrome, deficiency of the interleukin-1 receptor antagonist, and mevalonate kinase deficiency, for which anakinra is a known treatment., Results: We reported three off-label cardiorespiratory reasons to use IL-1Ra from our series: (i) chronic lung disease with pulmonary hypertension, (ii) interstitial lung disease with pulmonary hypertension to facilitate the weaning from respiratory support, and (iii) post-surgical polyserositis if effusions accumulate despite drainage. In all our patients, the drug was administered at a dosage of 10 mg/kg/day. The route of administration was chosen based on the patient's clinical characteristics, with the subcutaneous and intravenous routes being comparable in efficacy. The duration of therapy was modulated based on the patient's clinical response, with a minimum duration of 4 months. A total of 308 retrieved articles were screened, and then full texts of records deemed eligible for inclusion were assessed. Based on the literature search and our five cases, a total of 17 infants were treated with anakinra outside its approved indications. The major off-label use was for hemophagocytic lymphohistiocytosis/macrophage activation syndrome, followed by multisystem inflammatory syndrome in children and Kawasaki disease, as in two of our cases., Conclusions: According to the results of our case series and review of the literature, the off-label use of anakinra in neonates with inflammatory conditions refractory to first-line therapy could be considered. Prospective, multicenter research is necessary to determine whether anakinra is a safe treatment option for these infants to prevent early inflammatory illnesses and in which situations it could enhance clinical results., Competing Interests: Declarations. Funding: This work was supported by the Italian Ministry of Health with the Current Research funds. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics approval: This study reported only a retrospective analysis of data available through the institutional database. Personal data were restricted to essential information and were treated in order to guarantee the respect of the privacy of the involved patient, as specifically stated by Italian Law D. Lgs n.196 of 2003 about personal data protection. Therefore, the study did not require preliminary evaluation by the local ethical committee. The Scientific Director of “Bambino Gesù” Children’s Hospital IRCCS approved the publication of this manuscript (request Ronci Sara-RAP-2024-0004, date of approval: 09/07/2024). Consent to participate: All parents signed a written informed consent form before their children were subjected to intensive care, with the possibility of data relating to hospitalization being obtained anonymously and reproduced. Consent for publication: All parents signed a written informed consent form before their children were subjected to intensive care, with the possibility of data relating to hospitalization being obtained anonymously and reproduced. Availability of data and materials (data transparency): Not applicable. Code availability (software application or custom code): Not applicable. Author contributions: All authors were involved in writing the manuscript: DUDR designed the study, acquired and analyzed data from literature and patients’ data, and drafted the initial manuscript; FC designed the study, acquired and analyzed data from literature and patients’ data; CM, SR, SC, IS, IB, MPR and CA collected patients’ data and revised the manuscript; IC, PM, FDB, and AI critically reviewed the manuscript for important intellectual content; AD supervised the study and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work. All authors contributed to the article and approved the submitted version., (© 2025. The Author(s).)

Background: In the literature, there are no studies about the transfusion threshold for neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). In order to facilitate accurate interpretation of coagulation results in these neonates, we aimed to generate specific reference intervals in this specific population., Methods: This retrospective study included all HIE neonates admitted from 2014 to 2022 to undergo TH. All infants during TH underwent blood exams, including the coagulation profile. Our primary outcome was to assess the estimates of the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles for each parameter on admission (before transfusion). By the receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) and the best cut-off point were used to evaluate the ability of the prothrombin time expressed as international normalized ratio (PT-INR) to predict the risk of any bleeding., Results: A total of 143 infants were included in this study. On admission, the median fibrinogen value was 205 mg/dL, prothrombin time 18.6 seconds, PT-INR 1.50, activated partial thromboplastin time 38.3 seconds, thrombin time 18.6 seconds, antithrombin 57.0%. The optimal cut-off of PT-INR in predicting the risk of any bleeding was greater than 1.84 (AUC .623, p = .024)., Conclusion: For the first time, we proposed the percentiles of coagulation parameters in our cohort of neonates with HIE. Furthermore, we found that a PT-INR greater than 1.84 can significantly predict the risk of any bleeding. Further studies are needed to determine if a restrictive versus a liberal transfusion approach can be equally safer for these high-risk infants., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

In the last few years, current evidence has supported the use of point-of-care ultrasound (POCUS) for a number of diagnostic and procedural applications. Considering the valuable information that POCUS can give, we propose a standardized protocol for the management of neonates with a congenital diaphragmatic hernia (CDH-POCUS protocol) in the neonatal intensive care unit. Indeed, POCUS could be a valid tool for the neonatologist through the evaluation of 1) cardiac function and pulmonary hypertension; 2) lung volumes, postoperative pleural effusion or pneumothorax; 3) splanchnic and renal perfusion, malrotations, and/or signs of necrotizing enterocolitis; 4) cerebral perfusion and eventual brain lesions that could contribute to neurodevelopmental impairment. In this article, we discuss the state-of-the-art in neonatal POCUS for which concerns congenital diaphragmatic hernia (CDH), and we provide suggestions to improve its use. IMPACT: This review shows how point-of-care ultrasound (POCUS) could be a valid tool for managing neonates with congenital diaphragmatic hernia (CDH) after birth. Our manuscript underscores the importance of standardized protocols in neonates with CDH. Beyond the well-known role of echocardiography, ultrasound of lungs, splanchnic organs, and brain can be useful. The use of POCUS should be encouraged to improve ventilation strategies, systemic perfusion, and enteral feeding, and to intercept any early signs related to future neurodevelopmental impairment., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Herein, we present a newborn female with congenital vocal cord paralysis who required a tracheostomy in the neonatal period. She also presented with feeding difficulties. She was later diagnosed with a clinical picture of congenital myasthenia, associated with three variants of the MUSK gene: the 27-month follow-up was described. In particular, the c.565C>T variant is novel and has never been described in the literature; it causes the insertion of a premature stop codon (p.Arg189Ter) likely leading to a consequent formation of a truncated nonfunctioning protein. We also systematically collected and summarized information on patients' characteristics of previous cases of congenital myasthenia with neonatal onset reported in the literature to date, and we compared them to our case. The literature reported 155 neonatal cases before our case, from 1980 to March 2022. Of 156 neonates with CMS, nine (5.8%) had vocal cord paralysis, whereas 111 (71.2%) had feeding difficulties. Ocular features were evident in 99 infants (63.5%), whereas facial-bulbar symptoms were found in 115 infants (73.7%). In one hundred sixteen infants (74.4%), limbs were involved. Respiratory problems were displayed by 97 infants (62.2%). The combination of congenital stridor, particularly in the presence of an apparently idiopathic bilateral vocal cord paralysis, and poor coordination between sucking and swallowing may indicate an underlying congenital myasthenic syndrome (CMS). Therefore, we suggest testing infants with vocal cord paralysis and feeding difficulties for MUSK and related genes to avoid a late diagnosis of CMS and improve outcomes.

Introduction: The use of a lung ultrasound (LUS) score has been described in the early phases of neonatal respiratory distress syndrome; however, there is still no data regarding the application of the LUS score to neonates with a congenital diaphragmatic hernia (CDH). The objective of this observational cross-sectional study was to explore, for the first time, the postnatal changes in LUS score patterns in neonates with CDH, with the creation of a new specific CDH-LUS score. Methods: We included all consecutive neonates with a prenatal diagnosis of CDH admitted to our Neonatal Intensive Care Unit (NICU) from June 2022 to December 2022 who underwent lung ultrasonography. Lung ultrasonography (LUS) was determined at scheduled time points: (T0) during the first 24 h of life; (T1) at 24-48 h of life; (T2) within 12 h of surgical repair; (T3) a week after the surgical repair. We used a modified LUS score (CDH-LUS), starting from the original 0-3 score. We assigned 4 as a score in the presence of herniated viscera in the hemithorax (liver, small bowel, stomach, or heart in the case of a mediastinal shift) in the preoperative scans or pleural effusions in the postoperative scans. Results: We included in this observational cross-sectional study 13 infants: twelve/13 had a left-sided hernia (2 severe, 3 moderate, and 7 mild cases), while one patient had a right-sided severe hernia. The median CDH-LUS score was 22 (IQR 16-28) during the first 24 h of life (T0), 21 (IQR 15-22) at 24-48 h of life (T1), 14 (IQR 12-18) within 12 h of surgical repair (T2) and 4 (IQR 2-15) a week after the surgical repair (T3). The CDH-LUS significantly dropped over time from the first 24 h of life (T0) to a week after the surgical repair (T3), according to ANOVA for repeated measures. Conclusion: We showed a significant improvement in CDH-LUS scores from the immediate postoperative period, with normal ultrasonographic evaluations a week after surgery in most patients.

(1) Background: Massive social efforts to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have affected the epidemiological features of respiratory infections. (2) Methods: The study aims to describe the trend of hospitalizations for bronchiolitis among newborns and infants up to three months of life in Rome (Italy), in the pre-COVID-19 era and during the pandemic. (3) Results: We observed a marked decrease in the number of neonates and infants with bronchiolitis after national lockdowns in 2020 and the first months of 2021 and a similar trend in the number of bronchiolitis caused by respiratory syncytial virus (RSV). RSV was the leading pathogen responsible for bronchiolitis before the national lockdown in March 2020 (70.0% of cases), while Rhinovirus was the leading pathogen responsible for bronchiolitis (62.5%) during the pandemic while strict restrictions were ongoing. As Italy approached the COVID-19 vaccination target, the national government lifted some COVID-19-related restrictions. A surprising rebound of bronchiolitis (particularly cases caused by RSV) was observed in October 2021. (4) Conclusions: In this study, we describe for the first time the fluctuations over time of RSV bronchiolitis among newborns and young infants in Italy in relation to the restrictive measures containing the spread of the COVID-19 pandemic. Our results are in line with other countries' reports., Competing Interests: All data generated or analyzed during this study are included in this published article. Further inquiries can be directed to the corresponding author.

(1) Introduction: There is an increasing literature describing neonates born to mothers with SARS-CoV-2 infection (MIS-N) and infants infected with SARS-CoV-2 who presented with a severe disease (MIS-C). (2) Methods: To investigate clinical features of multisystem inflammatory syndrome in neonates and infants under six months of age, we used a systematic search to retrieve all relevant publications in the field. We screened in PubMed, EMBASE and Scopus for data published until 10 October 2021. (3) Results: Forty-eight articles were considered, including 29 case reports, six case series and 13 cohort studies. Regarding clinical features, only 18.2% of MIS-N neonates presented with fever; differently from older children with MIS-C, in which gastrointestinal symptoms were the most common manifestation, we displayed that cardiovascular dysfunction and respiratory distress are the prevalent findings both in neonates with MIS-N and in neonates/infants with MIS-C. (4) Conclusions: We suggest that all infants with suspected inflammatory disease should undergo echocardiography, due to the possibility of myocardial dysfunction and damage to the coronary arteries observed both in neonates with MIS-N and in neonates/infants with MIS-C. Moreover, we also summarize how they were treated and provide a therapeutic algorithm to suggest best management of these fragile infants.

Sepsis causes high rates of morbidity and mortality in NICUs. The estimated incidence varies between 5 and 170 per 1000 births, depending on the social context. In very low birth-weight neonates, the level of mortality increases with the duration of hospitalization, reaching 36% among infants aged 8-14 days and 52% among infants aged 15-28 days. Early diagnosis is the only tool to improve the poor prognosis of neonatal sepsis. Blood culture, the gold standard for diagnosis, is time-consuming and poorly sensitive. C-reactive protein and procalcitonin, currently used as sepsis biomarkers, are influenced by several maternal and fetal pro-inflammatory conditions in the perinatal age. Presepsin is the N-terminal fragment of soluble CD14 subtype (sCD14-ST): it is released in the bloodstream by monocytes and macrophages, in response to bacterial invasion. Presepsin seems to be a new, promising biomarker for the early diagnosis of sepsis in neonates as it is not modified by perinatal confounding inflammatory factors. The aim of the present review is to collect current knowledge about the role of presepsin in critically ill neonates.

Studies using videotape recordings and respiratory function monitoring have shown that both face mask (FM) application and endotracheal tube (ETT) placement represent a challenge for resuscitators. Hence, there is a strong need for devices that can largely be used independently of individual operator training levels, in order to ensure more reliable support in time-critical situations, such as neonatal resuscitation. The laryngeal mask airway device (LMA) has evolved as a potentially very valuable tool. We conducted a systematic review of studies evaluating the use of the LMA in neonatal resuscitation. An electronic literature search of large medical databases was performed to identify relevant publications on the use of an LMA during neonatal delivery room (DR) resuscitation. Following a rigorous systematic review, we identified a total of 7 randomized controlled trials with results indicating that initial respiratory management of newborn infants with an LMA is feasible for a defined subgroup of infants, but the evidence is still insufficient to recommend the LMA instead of FM ventilation in the DR. There is, in particular, a dearth of evidence of the use of LMA in neonates born before 34 weeks' gestational age or weighing <1,500 g at birth. There were no reports on significant complications following the use of LMA; however, evidence is still limited regarding short- and long-term outcomes. We conclude that the limited currently available evidence suggests that the use of the LMA is a feasible and safe alternative to mask ventilation of late preterm and term infants in the DR. The potential use of LMA resuscitation, in particular for low-gestation and low-birth-weight infants, needs further study., (© 2017 S. Karger AG, Basel.)

Unlabelled: As a result of increasing sport or car accident, straddle injuries in pediatric age are becoming increasingly frequent. Mild lesions of the external genitalia and urinary apparatus, are mainly observed in blunt trauma, whereas more severe lesions are reported in penetrating injuries; however, ano-rectal involvement alone, has been reported very rarely and especially in penetrating trauma. We describe herein a case of straddle trauma occurring in a 14yr old girl involved in a car accident. The girl reported anal sphincter rupture and rectal wall tear with a blunt mechanism. No other involvement of genitourinary apparatus was observed. The diagnostic and surgical approach of this rare consequence of a straddle, blunt injury are described and commented., Key Words: Anal sphincter rupture, Emergency laparoscopy, Perineal trauma, Rectal lesion, Straddle injury.

Background: Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements., Objective: The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth., Design: This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with ≥ 1 of the following morbidities: late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth., Results: We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 ± 5.6 g · kg⁻¹ · d⁻¹) and control (17.0 ± 8.7 g · kg⁻¹ · d⁻¹) groups (P = 0.478)., Conclusion: Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates. This trial was registered in the Australian New Zealand Clinical Trial Register as ACTRN12612000823875.

Aims: To analyze all evidence on the possible increase in morbidity and mortality determined by the use of inhibitors of gastric acid secretion (IGAS) drugs., Materials and Methods: We review all evidence exploring the adverse events associated with IGAS use in neonates., Results: Despite being prescribed in an off-label manner because of the perceived safety and potential benefit demonstrated for older populations, IGAS are being increasingly used in the neonatal period with much evidence derived from adults and children. Few data are available for neonates and indicate an association between IGAS use with infections and necrotizing enterocolitis (NEC), and with an increased mortality. Delayed gastric emptying, increased gastric mucus viscosity, modification in microbiota, and impairment of neutrophils functions are possible mechanisms of adverse events associated with IGAS use., Conclusions: A careful prescription of IGAS is crucial in order to reduce iatrogenic damage in neonates.