Veronica Notarbartolo

Background: Neonatal sepsis caused by multidrug-resistant (MDR) Gram-negative pathogens poses significant therapeutic challenges in neonatal intensive care units (NICUs), particularly in surgical neonates. Ceftazidime-avibactam (CAZ-AVI), a novel β-lactam/β-lactamase inhibitor combination, offers activity against extended-spectrum β-lactamases (ESBLs), AmpC, and serine carbapenemases, but neonatal experience remains limited. Methods and Results: We present a 35-week preterm neonate with long-gap esophageal atresia who developed late-onset sepsis caused by MDR Enterobacter hormaechei, including a KPC-producing carbapenem-resistant isolate, during postoperative recovery. After a multidisciplinary review, the patient received off-label CAZ-AVI at 25 mg/kg/dose (20/5 mg/kg) every 8 h, infused over 2 h, informed by available neonatal pharmacokinetic evidence and weight-adjusted dosing recommendations. Amikacin was administered contextually. Consecutive blood cultures obtained 48–72 h after dual antibiotic therapy initiation became negative and remained sterile, with concordant decline in inflammatory biomarkers, confirming rapid microbiological clearance. Unfortunately, the newborn died in the hours immediately following the final surgery performed to repair the esophageal atresia via end-to-end anastomosis; the cause was complications (hemothorax) unrelated to infectious diseases, although the onset of such severe sepsis may have compromised an already impaired immunological status. Discussion: This case shows mechanism-concordant antimicrobial selection and the feasibility of neonatal dosing when MDR Enterobacterales drive invasive infection. Our experience supports prospective evaluation of CAZ-AVI in carefully selected septic newborns while emphasizing the importance of rapid carbapenemase genotyping, susceptibility testing, and multidisciplinary oversight.

Background: The first 1000 days of life, from conception to 2 years of age, represent a critical window during which nutrition can exert long-lasting effects on neurodevelopment, immune maturation, and susceptibility to prematurity-related morbidity. Docosahexaenoic acid (DHA) is a key structural n-3 long-chain polyunsaturated fatty acid of the brain and retina, characterized by rapid fetal accretion during the third trimester. Methods: We conducted a narrative review of studies published from March 2015 up to December 2025, including randomized controlled trials, follow-up studies, and systematic reviews/meta-analyses about DHA supplementation during pregnancy, lactation, infancy and early childhood, and its role on development. Results: Across the first 1000 days, DHA supplementation improves biochemical DHA status, particularly in populations with low baseline levels (moderate to high level of evidence), while clinical outcomes remain heterogeneous. During pregnancy, some benefits in specific cognitive and behavioral domains have been demonstrated, whereas effects on global cognition and long-term behavior are frequently null (moderate evidence). Visual outcomes appear favorable, with improvements in visual acuity (moderate evidence). In preterm infants, enteral DHA—often combined with arachidonic acid (ARA)—is feasible and well tolerated. DHA may reduce inflammatory markers and necrotizing enterocolitis risk when in equilibrium with ARA (low to moderate evidence), while no evidence supports the link between DHA and reduced risk of bronchopulmonary dysplasia and retinopathy of prematurity (moderate evidence). Neurodevelopmental outcomes are mixed: neuroimaging studies suggest enhanced white matter maturation with DHA + ARA, whereas most trials show no clear benefit regarding standardized developmental scores (moderate evidence). Conclusions: DHA is biologically essential during the first 1000 days, but its clinical impact depends on timing, dose, baseline status, and prematurity-related context. The balance between DHA and ARA, rather than DHA supplementation alone, emerges as a key determinant of clinical efficacy, supporting a shift toward precision-based nutritional strategies in early life.

Background: The first 1000 days of life represent a critical window for developmental programming, during which specific nutritional exposures, such as vitamin D levels, may influence long-term health trajectories. Vitamin D plays a central role in skeletal development, but increasing evidence also supports its possible involvement in immune, metabolic, and neurodevelopmental processes during early life. In this narrative review, we summarize current evidence on the biological functions of vitamin D across the first 1000 days, focusing on its roles in skeletal, immune, metabolic, and neurodevelopmental processes, and its potential role as a programming factor. Methods: We conducted our research using the PubMed, Scopus, and Cochrane databases. We included systematic reviews, randomized controlled trials, and high-quality observational studies published from 2015 onward, focusing on pregnancy, neonatal life, and early childhood. Results: Vitamin D acts through placental, epigenetic, skeletal, immune, metabolic, and neurodevelopmental pathways that are particularly active during early development. Low maternal or early-life vitamin D status has been associated with adverse birth outcomes and impaired bone health. It has also been linked to increased susceptibility to infections and allergic diseases, altered metabolic trajectories, and mild neurodevelopmental differences. Evidence from supplementation trials remains heterogeneous, with benefits appearing more consistent in populations with baseline deficiency. Conclusions: Vitamin D fulfills several biological plausibility criteria for a potential early-life programming factor, although current human evidence remains heterogeneous.

Background: The increasingly indiscriminate use of antibiotic therapy in the neonatal period has led to the emergence of multidrug-resistant organisms (MDROs), which are responsible for sepsis that is increasingly difficult to treat and associated with high morbidity and mortality. Increasingly frequently, in neonatal intensive care units (NICUs), it is necessary to use last-generation antibiotics belonging to the RESERVE group according to the current classification of the World Health Organization (WHO). Methods: Among these drugs, ceftazidime-avibactam, ceftolozane-tazobactam and meropenem-vaborbactam are increasingly used in infections caused by Enterobacterales (i.e., E. cloacae complex, Klebsiella spp.), which are often responsible for late-onset sepsis (LOS) in newborns, especially in preterms. Results: Here, we present the experience of four newborn patients in the city of Palermo, treated over a period of 3 years. Conclusions: The comparison between different diagnostic–therapeutic management approaches and a review of the most recent literature can contribute to identifying more standardized pharmacological schemes, especially in the neonatal period, where scientific evidence about this topic is still very limited.

Background/Objectives: Neonatal esophageal perforation (EP) is a rare but potentially life-threatening condition, primarily affecting preterm and very low birth weight infants. Iatrogenic injury—most commonly related to malpositioned naso- or orogastric tubes—represents the leading cause. Methods: We conducted a comprehensive review of EP cases diagnosed within the first 28 days of life and reported between 2004 and October 2025 in PubMed and Scopus databases. The analysis focused on clinical presentation, risk factors, diagnostic modalities, management strategies, and outcomes. Only English-language case reports, case series, and observational studies (retrospective, cross-sectional and multicenter analyses) were included. Previously published narrative and systematic reviews were screened for relevant primary studies and contextual comparison, but were not included as primary data sources. Additionally, the emotional impact of iatrogenic complications on neonatal teams was also explored, through a focus on the importance of safety culture, reflective practice, and professional learning. Results: A total of 84 neonatal EP cases, were identified across 11 publications. The literature consistently indicates that iatrogenic EP predominantly affects infants born <28 weeks of gestational age and weighing <1000 g. Conservative management is effective in the majority of cases, whereas surgical intervention is reserved for complicated or refractory presentations. Prevention relies on standardized tube insertion techniques and early imaging verification. Conclusions: Although rare, neonatal EP demands high clinical vigilance, timely imaging-based diagnosis, and cautious conservative treatment. This review aims to consolidate available evidence while emphasizing the role of preventive strategies, safety culture, and team awareness in neonatal intensive care. By integrating clinical findings with reflections on iatrogenic risk, it seeks to support standardized practices, multidisciplinary learning, and continuous improvement in patient safety.

Background and Objectives: Primary vesicoureteral reflux (VUR) is a common pediatric urological disorder that can lead to significant renal morbidity if undetected or improperly managed. Ultrasound (US) plays a pivotal role in its assessment, providing a radiation-free tool to prenatal assessment, diagnosis, treatment, and long-term follow-up. This study aims to systematically review the literature on the use of US in pediatric primary VUR, emphasizing its applications in prenatal and postnatal diagnosis, intraoperative guidance, and follow-up monitoring. Methods: A systematic review of the literature was performed on PubMed in accordance with PRISMA guidelines. The research strategy used the following keywords: Ultrasound Vesicoureteral reflux, VUR Ultrasound, and VUR Sonography. A total of 2222 records were initially identified. After screening titles and abstracts for relevance, 2165 studies were excluded because they did not focus on ultrasound procedures, did not specify age limits, were redundant, involved non-homogeneous populations, or were unavailable in full text. Results: Prenatal US enables early identification of urinary tract anomalies suggestive of VUR, facilitating targeted postnatal evaluation. Postnatally, contrast-enhanced voiding ultrasound (CEVUS) offers a non-ionizing method for VUR confirmation or exclusion. Intraoperatively, US improves the accuracy and efficacy of bulking agent placement, potentially enhancing surgical outcomes. In follow-up, US remains essential for both conservatively managed and surgically treated patients, enabling timely detection of complications or recurrence. Conclusions: Ultrasound represents a useful tool in the management of pediatric primary VUR, applicable across all clinical stages, avoiding radiation exposure, and improving surgical effectiveness and follow-up management.

Background: Children’s interstitial and diffuse lung diseases, commonly referred to as “chILDs”, include around 200 rare conditions that disrupt normal lung function. They are classified, based on etiopathogenesis, into several subgroups, having a varied and multifaceted clinical presentation depending on the type of genetic mutation present. Methods and Results: We describe the case of a late preterm newborn presenting soon after birth with respiratory distress syndrome poorly responsive to surfactant administration, in whom a targeted gene panel analysis for pulmonary congenital diseases, performed using next-generation sequencing (NGS), revealed a novel compound heterozygous variant of the ATP-Binding-Cassette-Subfamily-A-Member-3 (ABCA3) gene. A review of the literature on the subject completes our work. Conclusions: Molecular genetic analysis has become crucial for a more targeted therapeutic treatment, along with the only current curative treatment option that is lung transplantation.

Background: In recent years, progress in the field of care has made prematurity an increasingly frequent phenomenon. The premature newborn, due to incompetence, is often subjected to parenteral nutrition (PN) for prolonged periods, and there may be several complications associated with it, first and foremost metabolic complications. Methods: In particular, the aim of this study was to evaluate how specific risk factors and/or auxological parameters influenced plasma variations in calcium, phosphorus, and magnesium levels. This is because, although little analyzed in the past, these electrolytes are essential for limiting the onset of unfavorable outcomes in neonatal age. This retrospective observational study was conducted by accessing the site intranet of the University Hospital “P. Giaccone” of Palermo, recruiting all newborns with PN necessities (106 in a total of 191), admitted to NICU in the period between 1 January 2020 and 1 January 2023. Infants undergoing PN through a central venous catheter (CVC), who remained in situ for a period ≥ 72 h, admitted to the NICU for the first time, were included. Infants with congenital malformations and/or deceased and/or transferred and/or without CVC or with CVC who remained in situ for a period < 72 h were excluded. We thus obtained 35 newborns in 2020, 33 newborns in 2021, and 38 newborns in 2022. Results: Hypophosphatemia was associated with a lower weight percentile (average 34.8 °C vs. 50.8 °C; p = 0.02) and a longer duration of PN (average 34.6 days vs. 17.3 days; p = 0.002). Newborns with hypercalcemia had, on average, lower gestational age (average 31.6 weeks vs. 35.7 weeks; p = 0.049) and weight at birth (average 1586 g vs. 2520 g; p = 0.038). Newborns with hypermagnesemia had, on average, higher weight and length (average weight percentile 62.1 °C vs. 42.7 °C; p = 0.038; average length percentile 66.7 °C vs. 44.4 °C; p = 0.003). Among the risk factors, cesarean section and undergoing surgery most influence the serum trend of the analyzed electrolytes. Conclusions: Although our results are partial and preliminary and have not always reached statistical significance, it is clear that dyselectrolytemias, in the context of metabolic complications PN-related, must be re-evaluated and carefully examined by the clinician. Prospective and controlled trials are needed to confirm our data, i.e., that the “calcium-phosphorus-magnesium axis” no longer plays only the niche role that was previously believed.

Background: Oxidative stress-related diseases in newborns arise from pro-oxidant/antioxidant imbalance in both term and preterm neonates. Pro-oxidant/antioxidant imbalance has shown to be present in different pathological conditions such as hypoxic ischemic encephalopathy (HIE), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA). Methods and Results: We performed a narrative review according to the most recent available literature (2012–2024), using Scopus and PubMed as electronic databases. Many observational and experimental studies in vitro and in vivo have evaluated the effectiveness of antioxidant therapies such as melatonin, erythropoietin (EPO), allopurinol, N-acetylcisteine (NAS), and nitric oxide synthase (NOS) inhibitors in these diseases. Perinatal asphyxia is one of the most important causes of mortality and morbidity in term and near-term newborns. Therapeutic hypothermia (TH) is the gold standard treatment for neonates with moderate-severe perinatal asphyxia, resulting in a reduction in the mortality and neurodevelopmental disability rates. Conclusions: According to the most recent literature and clinical trials, melatonin, allopurinol, NAS, NOS inhibitors, magnesium sulfate, and stem cells stand out as promising as both adjuvants and future probable alternatives to TH in the treatment of HIE.

The discovery of antimicrobial drugs has led to a significant increase in survival from infections; however, they are very often prescribed and administered, even when their use is not necessary and appropriate. Newborns are particularly exposed to infections due to the poor effectiveness and the immaturity of their immune systems. For this reason, in Neonatal Intensive Care Units (NICUs), the use of antimicrobial drugs is often decisive and life-saving, and it must be started promptly to ensure its effectiveness in consideration of the possible rapid evolution of the infection towards sepsis. Nevertheless, the misuse of antibiotics in the neonatal period leads not only to an increase in the development and wide spreading of antimicrobial resistance (AMR) but it is also associated with various short-term (e.g., alterations of the microbiota) and long-term (e.g., increased risk of allergic disease and obesity) effects. It appears fundamental to use antibiotics only when strictly necessary; specific decision-making algorithms and electronic calculators can help limit the use of unnecessary antibiotic drugs. The aim of this narrative review is to summarize the right balance between the risks and benefits of antimicrobial therapy in NICUs; for this purpose, specific Antimicrobial Stewardship Programs (ASPs) in neonatal care and the creation of a specific antimicrobial stewardship team are requested.