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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To examine birth characteristics that influence infant respiratory syncytial virus (RSV) hospitalisation risk in order to identify risk factors for severe RSV infections. Methods: Retrospective cohort study of 460 771 Sicilian children under 6 months old from January 2007 to December 2017. Hospital discharge records were consulted to identify cases and hospitalisations with International Classification of Diseases, Ninth Revision, Clinical Modification codes 466.11 (RSV bronchiolitis), 480.1 (RSV pneumonia) and 079.6 (RSV). RSV hospitalisation risk was estimated using adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Results: Overall, 2420 (5.25 per 1000 infants) RSV‐related hospitalisations were identified during the study, with girls accounting for 52.8%. RSV hospitalisation risk increased for full‐term, transferred, extreme immature, and preterm neonates with serious issues (aOR 3.25, 95% CI 2.90–3.64; aOR 1.86, 95% CI 1.47–2.32; aOR 1.54, 95% CI 1.11–2.07; and aOR 1.48, 95% CI 1.14–1.90). Compared to children born in June, the risk of RSV hospitalisation was significantly higher in children born in January (aOR 28.09, 95% CI 17.68–48.24) and December (aOR 27.36, 95% CI 17.21–46.99). Conclusion: This study identified birth month and diagnosis‐related groups as key predictors of RSV hospitalisations. This could help manage monoclonal antibody appropriateness criteria. [ABSTRACT FROM AUTHOR]

There is currently no worldwide agreement on the real need to administer conjunctival antibiotics to neonates at birth to prevent neonatal conjunctivitis (usually defined as ophthalmia neonatorum) by Chlamydia trachomatis and Neisseria gonorrhoeae. Therefore, there is wide variability in antibiotic administration, conditioned mainly by the social and health context. In Italy, a law enacted in 1940 required doctors and midwives to administer ophthalmic prophylaxis with 2% silver nitrate to all newborns at birth. This law was repealed in 1975 and since then there has been no clear guidance on the use of ophthalmia neonatorum prophylaxis at birth. Since neonatal conjunctivitis caused by C. trachomatis and N. gonorrhoeae is not reported, we carried out a nationwide survey of 1,041,384 neonates across all Italian birth centers to evaluate the incidence of ophthalmia neonatorum and the current practice of prophylaxis. After analyzing the results, we formulated an intersociety position statement on the prevention of ophthalmia neonatorum to update and standardize this prevention strategy in Italy. [ABSTRACT FROM AUTHOR]

Background: Allergic disease, including food allergies (FA)s, has been identified as a major global disease. The first 1000 days of life can be a "window of opportunity" or a "window of susceptibility", during which several factors can predispose children to FA development. Changes in the composition of the gut microbiota from pregnancy to infancy may play a pivotal role in this regard: some bacterial genera, such as Lactobacillus and Bifidobacterium, seem to be protective against FA development. On the contrary, Clostridium and Staphylococcus appear to be unprotective. Methods: We conducted research on the most recent literature (2013–2023) using the PubMed and Scopus databases. We included original papers, clinical trials, meta-analyses, and reviews in English. Case reports, series, and letters were excluded. Results: During pregnancy, the maternal diet can play a fundamental role in influencing the gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species via human milk oligosaccharides (HMOs), which play a prebiotic role. Moreover, complementary feeding can modify the gut microbiota's composition. Conclusions: The first two years of life are a critical period, during which several factors can increase the risk of FA development in genetically predisposed children. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is a topic of concern, especially in high-level care departments like neonatal intensive care units (NICUs). The systematic use of an "active" epidemiological surveillance system allows us to observe and analyze any changes in microbial distribution, limiting the risk of healthcare-associated infection (HAI) development. Methods: We have conducted a longitudinal observational study in the five NICUs of Palermo, comparing the "pre-pandemic period" (March 2014–February 2020) with the "pandemic" one (March 2020–February 2022). The primary aim of the study was to evaluate the cumulative prevalence of carriage from multi-drug resistant (MDR) bacteria in the cumulative NICUs (NICU C). Results: During the "pre-pandemic period", 9407 swabs were collected (4707 rectal, 4700 nasal); on the contrary, during the "pandemic period", a total of 2687 swabs were collected (1345 rectal, 1342 nasal). A statistically significant decrease in MDR-Gram-negative bacteria (GNB) carriage prevalence was detected during the pandemic. At the same time, there was a general worsening of the carriage of carbapenemase-forming MDR-GNB (CARBA-R+) and methicillin-resistant Staphylococcus aureus (MRSA) during the pandemic period. A significant reduction in methicillin-susceptible Staphylococcus aureus (MSSA) carriage was detected too. Conclusions: The surveillance of MDRO carriage in NICUs is fundamental for limiting the social and economic burden of HAIs. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate clinical, surgical, and genetic data of neonates with anorectal malformation (ARM). Study design: A retrospective observational study was conducted on neonates with ARM as an isolated type (group 1), with ≥2 (group 2), and with ≥3 associated malformations (group 3), born between 2009 and 2020. Distribution of ARM, associated abnormalities and genetic testing were analyzed, and risk factors for adverse outcomes were identified. Results: The 45 ARM cases (36% females) were divided as follows: 13 neonates belonging to group 1 (29%), 8 to group 2 (18%), and 24 to group 3 (53%). Cases were equally distributed over 11 years. Krickenbeck anatomy was: without fistula/imperforate anus (18%), perineal fistula (36%), rectourethral fistula (4%), rectovesical fistula (2%), vestibular fistula (4%), cloaca (4%), and rare ARMs (31%). Groups showed differences in anthropometric data, Krickenbeck anatomy, and intensive care burden. Additional major congenital abnormalities were prevalent specific of VATER/VACTERL spectrum (vertebral/anorectal/cardiac/tracheoesophageal/renal/limb defects), but also Hirschsprung disease was found in 3/20 biopsies (15%). The most frequent minor abnormality was a single umbilical artery. In group 3, we identified four de novo microdeletions at 8p23.2, 8q13.3, Xp22.31-p22.2, Xq28, four de novo microduplications at 1p36.32, 6p24.1-p23, 13q14.11, 15q11.2, one microdeletion at 9q33.1 inherited from the affected mother, one microdeletion at 7q35 inherited from the unaffected father, one structurally uncharacterized rearrangement involving 9p23-q34.3. Thus, we attributed the Xq28 deletion with inactivated FAM58A gene in one girl to the X-linked dominant STAR syndrome (toe syndactyly-telecanthus-anogenital/renal malformations). Conclusions: Despite the great physical and social burden on ARM patients and their parents, in the majority of cases, the etiology is largely unknown and attributed to be multifactorial. In females, STAR syndrome should be part of the differential diagnosis. Associated malformations of other organ systems interact in outcome parameters. [ABSTRACT FROM AUTHOR]

Respiratory tract infections (RTIs) are very common in children, especially in the first five years of life, and several viruses, such as the influenza virus, Respiratory Syncytial Virus, and Rhinovirus, are triggers for symptoms that usually affect the upper airways. It has been known that during respiratory viral infections, a condition of oxidative stress (OS) occurs, and many studies have suggested the potential use of antioxidants as complementary components in prophylaxis and/or therapy of respiratory viral infections. Preliminary data have demonstrated that antioxidants may also interfere with the new coronavirus 2's entry and replication in human cells, and that they have a role in the downregulation of several pathogenetic mechanisms involved in disease severity. Starting from preclinical data, the aim of this narrative review is to evaluate the current evidence about the main antioxidants that are potentially useful for preventing and treating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in adults and to speculate on their possible use in children by exploring the most relevant issues affecting their use in clinical practice, as well as the associated evidence gaps and research limitations. [ABSTRACT FROM AUTHOR]

Human milk contains a number of nutritional and bioactive molecules including microorganisms that constitute the so-called "Human Milk Microbiota (HMM)". Recent studies have shown that not only bacterial but also viral, fungal, and archaeal components are present in the HMM. Previous research has established, a "core" microbiome, consisting of Firmicutes (i.e., Streptococcus, Staphylococcus), Proteobacteria (i.e., Serratia, Pseudomonas, Ralstonia, Sphingomonas, Bradyrhizobium), and Actinobacteria (i.e., Propionibacterium, Corynebacterium). This review aims to summarize the main characteristics of HMM and the role it plays in shaping a child's health. We reviewed the most recent literature on the topic (2019-2021), using the PubMed database. The main sources of HMM origin were identified as the retrograde flow and the entero-mammary pathway. Several factors can influence its composition, such as maternal body mass index and diet, use of antibiotics, time and type of delivery, and mode of breastfeeding. The COVID-19 pandemic, by altering the mother-infant dyad and modifying many of our previous habits, has emerged as a new risk factor for the modification of HMM. HMM is an important contributor to gastrointestinal colonization in children and therefore, it is fundamental to avoid any form of perturbation in the HMM that can alter the microbial equilibrium, especially in the first 100 days of life. Microbial dysbiosis can be a trigger point for the development of necrotizing enterocolitis, especially in preterm infants, and for onset of chronic diseases, such as asthma and obesity, later in life. [ABSTRACT FROM AUTHOR]

This study was aimed to analyze the commonalities and distinctions of voltage‐gated sodium channels, Nav1.2, Nav1.6, in neurodevelopmental disorders. An observational study was performed including two patients with neurodevelopmental disorders. The demographic, electroclinical, genetic, and neuropsychological characteristics were analyzed and compared with each other and then with the subjects carrying the same genetic variants reported in the literature. The clinical features of one of them argued for autism spectrum disorder and developmental delay, the other for intellectual disability, diagnoses confirmed by the neuropsychological assessment. The first patient was a carrier of SCN2A (p.R379H) variant while the second was carrier of SCN8A (p.E936K) variant, both involving the pore loop of the two channels. The results of this study suggest that the neurodevelopmental disorders without overt epilepsy of both patients can be the consequences of loss of function of Nav1.2/Nav1.6 channels. Notably, the SCN2A variant, with an earlier expression timing in brain development, resulted in a more severe phenotype as autism spectrum disorder and developmental delay, while the SCN8A variant, with a later expression timing, resulted in a less severe phenotype as intellectual disability. [ABSTRACT FROM AUTHOR]

Introduction The Tousled-like kinases 1 and 2 (TLK1 and TLK2) are involved in many fundamental processes, including DNA replication, cell cycle checkpoint recovery and chromatin remodelling. Mutations in TLK2 were recently associated with 'Mental Retardation Autosomal Dominant 57' (MRD57, MIM# 618050), a neurodevelopmental disorder characterised by a highly variable phenotype, including mild-to-moderate intellectual disability, behavioural abnormalities, facial dysmorphisms, microcephaly, epilepsy and skeletal anomalies. Methods We re-evaluate whole exome sequencing and array-CGH data from a large cohort of patients affected by neurodevelopmental disorders. Using spatial proteomics (BioID) and single-cell gel electrophoresis, we investigated the proximity interaction landscape of TLK2 and analysed the effects of p.(Asp551Gly) and a previously reported missense variant (c.1850C>T; p.(Ser617Leu)) on TLK2 interactions, localisation and activity. Results We identified three new unrelated MRD57 families. Two were sporadic and caused by a missense change (c.1652A>G; p.(Asp551Gly)) or a 39 kb deletion encompassing TLK2, and one was familial with three affected siblings who inherited a nonsense change from an affected mother (c.1423G>T; p.(Glu475Ter)). The clinical phenotypes were consistent with those of previously reported cases. The tested mutations strongly impaired TLK2 kinase activity. Proximal interactions between TLK2 and other factors implicated in neurological disorders, including CHD7, CHD8, BRD4 and NACC1, were identified. Finally, we demonstrated a more relaxed chromatin state in lymphoblastoid cells harbouring the p.(Asp551Gly) variant compared with control cells, conferring susceptibility to DNA damage. Conclusion Our study identified novel TLK2 pathogenic variants, confirming and further expanding the MRD57-related phenotype. The molecular characterisation of missense variants increases our knowledge about TLK2 function and provides new insights into its role in neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a typical disorder of preterm newborns, with a high mortality and morbidity rate. The therapeutic and nutritional management of disease depends on several factors. Its prognosis is linked, in addition to the severity of the disease and the need for surgery, to a correct enteral feeding in these patients. This study aims to identify the clinical characteristics of 18 patients with NEC, evaluating the different therapeutic paths undertaken, the type of formula used and the survival rate of this population. Average time of enteral nutrition before the NEC onset was 11,3 ± 11,6 days, with an average fasting period since the onset of 24 ± 18.9 days. 77.8% of patients received surgery and resumed enteral nutrition 17.7 ± 17.9 days after the intervention. The overall survival rate of our cohort was 55.5%. More prospective studies are needed to evaluate the long-term outcomes of survived children with NEC. [ABSTRACT FROM AUTHOR]

Background: The lives of many children and adolescents are today increasingly influenced by new technological devices, including smartphones. The coronavirus disease 2019 (COVID-19) pandemic occurred in a time of outstanding scientific progress and global digitalization. Young people had relevant adverse psychological and behavioral effects due to the COVID-19 pandemic, mainly related to infection control measures, which led them to spend more time at home and with major use of technological tools. The goal this study proposes is to evaluate health and social outcomes of smartphone overuse among Italian children and adolescents during the COVID-19 pandemic, analyzing patterns and aims of utilization, as well as the eventual presence and degree of addiction. Methods: This study was based on a self-report and anonymous questionnaire, which was administered to 184 Italian school-age (6–18 years) children and adolescents during the second wave of the COVID-19 pandemic. The test was electronically (email, whatsapp) explained and sent by pediatricians either directly to older children (middle and high school), or indirectly, through the help of teachers, to younger ones (primary school). All participants spontaneously and voluntarily joined the present study. The survey was made by 4 sections, and designed to know and outline modalities (frequency, patterns and aims) of smartphone use, adverse outcomes, and related parental behaviors, also in order to reveal the eventual occurrence and degree of addiction. The same information, related to the pre-epidemic period, was also investigated and analyzed. Results: The data obtained revealed a significantly greater adhesion to the questionnaire by females, likely reflecting higher attention and interest than boys to initiatives relating to health education. Our study showed more frequent smartphone use among Italian children and adolescents during the COVID-19 pandemic, compared to the pre-epidemic period. This may be related to the social distancing measures adopted during the months under investigation. The present survey also outlined the changing patterns and aims in the use of smartphones among young people, which allowed to limit some effects of the crisis. Indeed, they were used for human connection, learning and entertainment, providing psychological and social support. Finally, it was observed a significant increase of overuse and addiction. This led to many clinical (sleep, ocular and musculoskeletal disorders), psychological (distraction, mood modification, loss of interest) and social (superficial approach to learning, isolation) unfavorable outcomes. Conclusions: Pediatricians and health care professionals should be aware of the potential risks related to inappropriate use of smartphones. They should monitor, in cooperation with parents, possible associated adverse effects, in order to early recognize signs and symptoms suggestive, or at high risk, for addiction. They must carry out, as well, the necessary interventions to prevent and/or lower the detrimental impact of smartphone overuse on children and adolescents' health, oriented to sustain adequate physical and psychological development as well as social relationships. [ABSTRACT FROM AUTHOR]

Introduction: In 1973, Petrea Jacobsen described the first patient showing dysmorphic features, developmental delay and congenital heart disease (atrial and ventricular septal defect) associated to a 11q deletion, inherited from the father. Since then, more than 200 patients have been reported, and the chromosomal critical region responsible for this contiguous gene disorder has been identified. Patients' presentation: We report on two unrelated newborns observed in Italy affected by Jacobsen syndrome (JBS, also known as 11q23 deletion). Both patients presented prenatal and postnatal bleeding, growth and developmental delay, craniofacial dysmorphisms, multiple congenital anomalies, and pancytopenia of variable degree. Array comparative genomic hybridization (aCGH) identified a terminal deletion at 11q24.1-q25 of 12.5 Mb and 11 Mb, in Patient 1 and 2, respectively. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletion for Patient 1; parents of Patient 2 refused further genetic investigations. Conclusions: Present newborns show the full phenotype of JBS including thrombocytopenia, according to their wide 11q deletion size. Bleeding was particularly severe in one of them, leading to a cerebral hemorrhage. Our report highlights the relevance of early diagnosis, genetic counselling and careful management and follow-up of JBS patients, which may avoid severe clinical consequences and lower the mortality risk. It may provide further insights and a better characterization of JBS, suggesting new elements of the genotype-phenotype correlations. [ABSTRACT FROM AUTHOR]

We describe an additional newborn with craniofacial dysmorphisms, congenital heart disease, hypotonia, and a 2q13 deletion of 1.7 Mb. The clinical and genomic findings observed are consistent with the diagnosis of 2q13 microdeletion syndrome. [ABSTRACT FROM AUTHOR]

Maternal milk represents the best food for the newborn, providing specific physiologic advantages over the other sources of nutrition. It also contains many hundreds to thousands of bioactive molecules that protect against infection (i.e. IgA), inflammation (i.e. 5-methylthioadenosine) and contribute to eliciting strong immune responses in breastfed children (i.e. allergens or viral antigens). Quality and quantity of breast milk components may influence the development of infant body composition in the first years of life; in particular, it has been shown that a different composition of human oligosaccharides (HMOs) in overweight/obese women's human milk can be correlated with her offspring's growth. This could be associated with human milk's probiotic role, since probiotics support the assembly of a healthy gut microbiome, by stimulating the growth of beneficial microbes. Therefore, the aim of this review is to outline the bioactive role of human milk and its potential beneficial effect on a child's long-term health. [ABSTRACT FROM AUTHOR]