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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]

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]

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]