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ENGLISH TEXT Introduction and state of the art: Adolescence is an age characterized – as is well known – by sudden changes at the physical and psycho-cognitive levels, in which adolescents go through complex phases in which affective, emotional and especially social-relational difficulties are intertwined. The most recent orientations in developmental psychology, however, have shifted the focus of the approach to this fundamental phase of development, hitherto framed in the “critical” perspective of difficulties and stress to overcome. By adopting the paradigm of positive psychology, attention can be focused on good practices functional to the promotion of individual well-being, through training that starts from the acquisition of greater self-awareness and the potential to be implemented in order to achieve one’s own well-being (psychological well-being) and, therefore, “happiness”, a term used here net of the legitimate questions that such a complex state of mind poses in order to its very precise definition. Even in the ministerial guidelines of education in several European countries, including Italy, there is now a reversal of the previous promotion of a digital school and e-learning model, pointing to a general reduction in the use of electronic devices (PCs, tablets and cell phones) for educational purposes, in favor of more traditional forms and environments of learning, centered on cooperative learning and social learning. Project goals: The purpose of the project is to monitor and evaluate the psychological well-being of students, as well as the usefulness of the impact, for this purpose, of the mediation of a communicative model based on direct relationship with a public figure in the school context. Regarding the first point, it is intended to administer, adapting it appropriately, the Oxford Happiness Questionnaire (OHQ), an instrument used to detect the degree of happiness and subjective well-being of individuals. In the implementation of monitoring and of useful interventions in the pursuit of adolescents’ well-being within the educational context, it is believed that a key and innovative role can be played by the active participation in the project of a reference figure for young people, such as a person from outside the school world, with his own successful human and professional educational experience, who offers young people a positive model of dialogue and direct confrontation. The goal is to complement and enrich the socio-affective interaction with adolescents with concrete and direct human input, not mediated by social media. In this direction, the testimony of one of the most sought-after and established international supermodels, known as a “beauty ambassador with a human side,” engaged in volunteer work, philanthropic activities and collaborative projects in various school contexts and in pediatric long-term care wards, can help foster dialogue with adolescents and the exchange of experiences, expectations and ideas useful in overcoming those critical factors that hinder the well-being and serenity of adolescents, especially in contexts of social marginality and educational poverty. Type of intervention, materials and methods: The beneficiaries of the project are preadolescents and adolescents, and the planned interventions are implemented within schools, as places not only of curricular education, but understood as primary places of community life, socialization and protection of the health and mental and physical well-being of adolescents. The project involves the administration of the OHQ appropriately adapted to students in Italian schools participating in the Adolescent Well-Being School Project. The objective of this questionnaire is to measure happiness in general, that is, psychological well-being. If the OHQ can now boast of an effective use proven by a large number of studies in numerous countries, including non-European ones, the novelty of the present proposal consists mainly in the innovation of the administration context, through a different communicative model, which, playing intentionally with the term that gives the project its title, can also be represented by a supermodel in the role of mediator and facilitator of some phases of the action itself. This choice, as well as being original, is deliberately antithetical to the current trend, which privileges, especially in operations of this type and, more generally, in the context of the daily lives of adolescents, virtual and media relationships, with all the risks of socio-relational deprivation that have already been mentioned and which are, moreover, before everyone’s eyes. The choice therefore falls on a mediating figure who can at the same time offer a concrete and evident testimony to a state of well-being that is also physical, insofar as it comes from a healthy lifestyle, in which, of course, care for nutrition and regular exercise practiced without excesses are included. Expected results: The ultimate goal is the diffusion and dissemination, among adolescents, of good practices of real and direct, healthy and constructive relationships, both in the peer relationship and in the relationship with family, educational institutions and society. The perspective is to provide support for the development and maturation, as early as adolescence, of skills and attitudes for the construction and maintenance of ongoing individual well-being, a perspective where the individual and autonomous propensity for lifelong learning is also complemented by the fundamental one for lifelong well-being. ITALIAN TEXT Introduzione e stato dell’arte: L’adolescenza è un’età caratterizzata – come è noto – da repentini cambiamenti a livello fisico e psico-cognitivo, in cui i ragazzi attraversano fasi complesse nelle quali s’intrecciano difficoltà affettive, emotive e soprattutto socio-relazionali. I più recenti orientamenti della psicologia dell’età evolutiva hanno però spostato il focus dell’approccio a questa fase fondamentale dello sviluppo, finora inquadrata nella prospettiva “critica” delle difficoltà e dello stress da superare. Adottando il paradigma della positive psychology, l’attenzione può essere puntata su buone prassi funzionali alla promozione del benessere individuale, attraverso un training che parte dall’acquisizione di una maggiore consapevolezza di sé e delle potenzialità da attuare al fine del raggiungimento del proprio benessere (psychological well-being) e, quindi, della “felicità”, termine adoperato qui al netto delle legittime questioni che uno stato dell’animo così complesso pone in ordine a una sua definizione ben precisa. Anche negli orientamenti ministeriali dell’istruzione in diversi paesi europei, compresa l’Italia, si assiste oggi a un’inversione di tendenza rispetto alla precedente promozione di un modello di scuola digitale e di e-learning, puntando a una riduzione generale dell’impiego dei dispositivi elettronici (pc, tablet e cellulari) a fini didattici, a favore di forme e ambienti di apprendimento più tradizionali, incentrati sul cooperative learning e l’apprendimento sociale. Obiettivi del progetto: Scopo del progetto è monitorare e valutare il benessere psicologico degli studenti, nonché l’utilità dell’impatto, a tal fine, della mediazione di un modello comunicativo fondato sulla relazione diretta con un personaggio pubblico nel contesto scolastico. Per quanto concerne il primo punto, s’intende somministrare, adattandolo opportunamente, l’Oxford Happiness Questionnaire (OHQ), strumento utilizzato per rilevare il grado di felicità e benessere soggettivo degli individui. Nell’attuazione del monitoraggio e di interventi utili al perseguimento del benessere degli adolescenti nell’ambito del contesto formativo, si ritiene che possa svolgere un ruolo chiave e innovativo la partecipazione attiva al progetto di una figura di riferimento per i giovani, quale può considerarsi un soggetto esterno al mondo della scuola, con una propria esperienza formativa umana e professionale di successo, che offra ai ragazzi un modello positivo di dialogo e confronto diretto. L’obiettivo è quello di integrare e arricchire l’interazione socioaffettiva con gli adolescenti di un apporto umano concreto e diretto, non mediato dai social media. In tale direzione, la testimonianza di un top model fra i più ricercati e affermati a livello internazionale, noto come “beauty ambassador dal lato umano”, impegnato nell’ambito del volontariato, in attività filantropiche e in progetti di collaborazione in diversi contesti scolastici e nei reparti pediatrici di lungodegenza, può contribuire a favorire il dialogo con gli adolescenti e lo scambio di esperienze, aspettative e idee utili al superamento di quei fattori di criticità che ostano al benessere e alla serenità degli adolescenti, soprattutto in contesti di marginalità sociale e di povertà educativa. Tipologia d’intervento, materiali e metodi: I soggetti beneficiari del progetto sono i preadolescenti e gli adolescenti, e gli interventi previsti sono attuati all’interno delle scuole, quali presidi non solo della formazione curricolare, ma intese come luoghi primari di vita comunitaria, di socializzazione e di tutela della salute e del benessere psico-fisico degli adolescenti. Il progetto prevede la somministrazione dell’OHQ opportunamente adattato agli studenti delle scuole italiane che aderiscono all’Adolescent Well-Being School Project. L’obiettivo di questo questionario è misurare la felicità in generale, cioè il benessere psicologico. Se l’OHQ può vantare ormai un impiego efficace e comprovato da una nutrita serie di studi in numerosi paesi anche extra-europei, la novità della presente proposta consiste principalmente nell’innovazione del contesto di somministrazione, attraverso un diverso modello comunicativo, che, giocando volutamente con il termine che dà il titolo al progetto, può essere rappresentato anche da un top model in veste di mediatore e facilitatore di alcune fasi dell’azione stessa. Tale scelta, oltre che originale, è volutamente antitetica all’attuale tendenza, che privilegia, soprattutto in operazioni di questo tipo e, più in generale, nel contesto della vita quotidiana degli adolescenti, le relazioni virtuali e mediatiche, con tutti i rischi di deprivazioni socio-relazionali cui si è già accennato e che sono, del resto, sotto gli occhi di tutti. La scelta ricade perciò su una figura di mediazione che possa al tempo stesso offrire una testimonianza concreta ed evidente di uno stato di benessere che è anche fisico, in quanto riveniente da un regime di vita sano, in cui naturalmente rientrano la cura dell’alimentazione e un esercizio fisico regolare e praticato senza eccessi. Risultati attesi: L’obiettivo finale è la diffusione e disseminazione, fra gli adolescenti, di buone prassi di relazioni reali e dirette, sane e costruttive, sia nel rapporto tra pari sia nel rapporto con la famiglia, le istituzioni formative e la società. La prospettiva è quella di fornire un supporto allo sviluppo e alla maturazione, sin dall’adolescenza, di capacità e attitudini alla costruzione e al mantenimento di un benessere individuale costante, una prospettiva che alla propensione individuale e autonoma al lifelong learning affianchi anche quella imprescindibile al lifelong well-being.

Assisted reproductive technology (ART) is an emerging field in medicine that incorporates complex procedures and has profound ethical, moral, social, religious, and economic implications not just for the individuals who have access to this method but also for society. In this narrative review, we summarise multiple aspects of ART procedures and the possible consequences on the mother and newborn. Moreover, we provide an overview of the possible long-term consequences of ART procedures on the health of newborns, although longitudinal evidence is particularly scant. Users should be informed that ART procedures are not risk-free to prepare them for the possible negative outcomes that may occur in the perinatal period or even in childhood and adulthood. Indeed, risk estimates point to increased liability for major nonchromosomal birth defects; cardiovascular, musculoskeletal, and urogenital (in male newborns) defects; and any other birth defects. Less certainty is present for the risk of neuropsychiatric sequelae in children conceived through ART. Thus, its application should be accompanied by adequate counselling and psychological support, possibly integrated into specific multidisciplinary clinical programmes.

Exposure to endocrine-disrupting chemicals (EDCs) is inevitable, and growing scientific evidence indicates that even very low doses can negatively impact human health, particularly during pregnancy and the neonatal period. As part of the European project LIFE18 ENV/IT/00460, this study aims to identify the presence of EDCs in 20 infant formulas (both powdered and liquid) and the release from baby bottles and teats. Particularly, sensitization of young people and future parents towards the potential harmful effects of EDCs could significantly help to reduce exposure. Seven different UPLC-MS/MS methodologies and one ICP-AES were set up to quantify already assessed and suspected EDCs among 85 different chemicals (bisphenols, parabens, PAHs, phthalates, pesticides, herbicides and their main metabolites, PFAS, and metals). Results showed that in 2 out of 14 baby bottles, only anthracene and phenanthrene of the group of PAHs were released (10.68–10.81 ng/mL). Phthalates such as mono-ethyl phthalate (MEP) were found in 9 of 14 samples (0.054–0.140 ng/mL), while mono(2-ethyl-5-oxohexyl) phthalate (MeOHP) appeared in 2 samples (0.870–0.930 ng/mL). In accordance with current EU regulations, other chemicals were not detected in baby bottles and teats. However, bisphenols, parabens, PAHs, phthalates, PFAS, and metals were detected in infant formula, emphasizing the need for continued monitoring and public health interventions.

Recent findings of stem/progenitor cells in maternal milk and their ability to cross the intestinal barrier of lactating newborns and integrate into neonatal organs to promote optimal child development present a new challenge in perinatal medicine. These findings emphasize the need for all mothers to breastfeed their babies for a long time. According to recent research, breastfeeding protects the lactating newborn from multiple infectious agents that can cause severe and fatal early infancy diseases. The second benefit is that maternal stem cells accelerate the development of several organs, including the brain, protecting lactating infants from severe childhood and adult diseases. The success and diffusion of exclusive breastfeeding, especially in low-resource settings, depends on mothers' knowledge of the many benefits for their child, including recent discoveries on breastfeeding's powerful benefits. Every mother may need simple booklets to learn about the unique benefits of maternal breastfeeding, including the nutrients and multiple cell types that protect the newborn from infections and accelerate neonatal organ development. Social media should also be encouraged to spread news about breastfeeding and maternal stem cells' impact on lactating infants' health. Health belief model interventions may boost breastfeeding. In conclusion, the discovery of massive amounts of cells in maternal milk and the identification of stem/progenitors with previously unknown potential in newborn development after birth should be considered a new valuable tool for exclusive breastfeeding advocates. Data here suggests that every action to spread this message and educate mothers and families about breastfeeding's irreplaceable role is mandatory.

This comprehensive review synthesizes the wealth of scientific literature pertaining to the application of Artificial Intelligence (AI) in the field of metabolomics. Over the past decade, AI has played an increasingly pivotal role in deciphering the complexities of metabolomic data, offering novel insights into the molecular underpinnings of biological systems. Through an extensive examination of relevant research papers, we provide a comprehensive overview of the diverse AI techniques and methodologies, from data preprocessing and feature selection to predictive modeling and pathway analysis, employed in metabolomics studies. The review dissects key trends and advancements in AI-driven metabolomics, shedding light on its pivotal role in biomarker discovery, disease diagnosis, and personalized medicine. In addition to highlighting the significant contributions of AI to metabolomics, emerging frontiers will be explored, such as the incorporation of multi-omics data integration and the growing importance of explainable AI in biological research. Ultimately, this review underscores the transformative impact of AI on metabolomics, emphasizing its potential to reshape our understanding of metabolic pathways, disease mechanisms, and therapeutic interventions. The combination of AI and metabolomics stands as a powerful paradigm shift with far-reaching implications for advancing both fundamental scientific knowledge and practical applications across diverse domains.

Dear Readers, I would like to share with you the news that, in November 2023, the Journal of Pediatric and Neonatal Individualized Medicine (JPNIM) was awarded a “Journal of high cultural value” prize by the Italian Ministry of Culture, through the General Directorate for Libraries and Copyright (with the decree D.D.G. n. 812, 16/11/2023). This is a great achievement as, in the biological-medical field, only a total of 3 journals were awarded by this decree. This Editorial shows information about JPNIM, JPNIM Open Access policy, JPNIM Editorial Board, JPNIM indexing and archiving, the fact that JPNIM is the official journal of many Societies, JPNIM publication, JPNIM website views and JPNIM metrics.

One of the most frequent triggers of food anaphylaxis in pediatric age but also among the most common, early, and complex causes of childhood food allergy is cow’s milk protein allergy (CMPA). The diagnostic course and management of this allergy is defined in a complex clinical picture due to several factors. First of all, the epidemiological data are not uniform, mainly as a consequence of the diagnostic methodology used in the various studies and the different age ranges covered. In addition, there is the complexity of terminology, since although CMPA traditionally refers to immune-mediated reactions to cow’s milk, it is a term encompassing numerous clinical features with different symptoms and the requirement for specific treatments. Moreover, the differential diagnosis with other very frequent diseases, especially in the first year of life, such as gastro-esophageal reflux disease or colic, is still complex. This can result in misdiagnosis and incorrect treatment, with harmful health consequences and significant economic repercussions. In this context, the combination of several omics sciences together, which have already proved useful in clarifying the allergenicity of cow’s milk proteins with greater precision, could improve the diagnostic tests currently in use through the identification of new, more specific, and precise biomarkers that make it possible to improve diagnostic accuracy and predict the patient’s response to the various available treatments for the recovery of tolerance.

Postpartum depression (PD) is the most widespread perinatal psy­chiatric disorder, also representing the most frequent non-obstetric birth-related complication. From an epidemiological point of view, it has an average prevalence of 17-18% worldwide. This psychiatric disorder may have long-standing effects on the health of both the mother and the child, but also on the relationship with the partner (including paternal PD). Therefore, an early diagnosis is fundamental to treat this disorder immediately and avoid such complications. Talking About, by the company GPI (Trento, Italy), is a project focused on voice analysis as a medium to access human emotions. It consists of a series of Speech Emotion Recognition (SER) algorithms. The aim of the study is to evaluate the application of the artificial intelligence (AI) algorithm Talking About on the mothers’ emotions analysis. Talking About investigates the unconscious aspects of voice that usually cannot be controlled or voluntarily modified, aiming at identifying the subjects’ emotions. Thus, all bias, characterising all classic screening questionnaires, should be neutralised, achieving a sharper overview of the mothers’ emotional state. The mother’s emotional results are displayed in 5 main categories: 2 positive, 3 negative. This study has engaged a total of 154 mothers who gave birth at the “Policlinico Universitario D. Casula” and/or carried out a pediatric examination at the “ambulatorio SOS MAMI” (which is a PostNatal Care Service). They underwent both the Edinburgh Postnatal Depression Scale (EPDS) test and the Talking About voice test. Despite this study’s sample limitations, our preliminary data related to PD symptoms identification are promising and encouraging, leading the way to further investigations related to the application of AI as a PD screening support. Indeed, further studies are needed to improve our knowledge on this topic and possibly apply this tool in clinical practice in the future, even considering PD of the father.

The skin is a complex ecosystem colonized by millions of microorganisms, the skin microbiota, which are crucial in regulating not only the physiological functions of the skin but also the metabolic changes underlying the onset of skin diseases. The high microbial colonization together with a low diversity at the phylum level and a high diversity at the species level of the skin is very similar to that of the gastrointestinal tract. Moreover, there is an important communication pathway along the gut–brain–skin axis, especially associated with the modulation of neurotransmitters by the microbiota. Therefore, it is evident that the high complexity of the skin system, due not only to the genetics of the host but also to the interaction of the host with resident microbes and between microbe and microbe, requires a multi-omics approach to be deeply understood. Therefore, an integrated analysis, with high-throughput technologies, of the consequences of microbial interaction with the host through the study of gene expression (genomics and metagenomics), transcription (transcriptomics and meta-transcriptomics), and protein production (proteomics and meta-proteomics) and metabolite formation (metabolomics and lipidomics) would be useful. Although to date very few studies have integrated skin metabolomics data with at least one other ‘omics’ technology, in the future, this approach will be able to provide simple and fast tests that can be routinely applied in both clinical and cosmetic settings for the identification of numerous skin diseases and conditions. It will also be possible to create large archives of multi-omics data that can predict individual responses to pharmacological treatments and the efficacy of different cosmetic products on individual subjects by means of specific allotypes, with a view to increasingly tailor-made medicine. In this review, after analyzing the complexity of the skin ecosystem, we have highlighted the usefulness of this emerging integrated omics approach for the analysis of skin problems, starting with one of the latest ‘omics’ sciences, metabolomics, which can photograph the expression of the genome during its interaction with the environment.

Benign paroxysmal positional vertigo (BPPV) represents the most frequent cause of peripheral vertigo. In most cases, it is successfully treated using the canalith repositioning procedure, but it is often followed by continuous lightheadedness in the absence of vertigo or nystagmus (residual dizziness, RD). Our aim is to describe the clinical effectiveness and the urine metabolomics profile of treating these patients with polyphenol compound supplementation. We enrolled 30 patients reporting RD after BPPV of the posterior semicircular canal (PSC) successfully treated using the Semont maneuver. Supplementation with a polyphenol compound was administered for 60 days, and patients were evaluated after 30 and 60 days of treatment using self-administered questionnaires (Visual Analog Scales for Dizziness and Nausea, Dizziness Handicap Inventory, DHI) and urine metabolomics analysis performed using 1H-NMR spectroscopy and multivariate followed by univariate analysis. Most patients reported excellent or good efficacy in the treatment of RD with a significant decrease in VAS and DHI values. The metabolomics analysis identified six significant metabolites related to the treatment, namely 1-methylnicotinamide, anserine, hippurate, lysine, methyl succinate and urea, indicating the inflammatory activities and antioxidant properties of the polyphenol compound. These preliminary data suggest that supplementation with a polyphenol compound could induce some metabolic changes that can help in recovery from RD. However, future steps will require confirmation with a more significant cohort of patients and an extension of the metabolomics evaluation to other problems concerning the different clinical aspects of BPPV, such as the high rate of relapse.

Abstract Background Long COVID-19 syndrome is a complex of symptoms that occurs after the acute SARS-CoV-2 infection, in the absence of other possible diagnoses. Studies on Long COVID-19 in pediatric population are scanty and heterogeneous in design, inclusion criteria, outcomes, and follow-up time. The objective of the present study is to assess the prevalence of Long COVID-19 syndrome in a cohort of Italian pediatric primary care patients, observed for a period of time of 8 to 36 weeks from healing. Prevalence was also assessed in a cohort of pediatric patients hospitalized during acute infection. Methods Data concerning 629 primary care patients with previous acute SARS-CoV-2 infection were collected by a questionnaire filled in by Primary Care Pediatrician (PCP). The questionnaire was administrated to patients by 18 PCPs based in 8 different Italian regions from June to August 2021. Data concerning 60 hospitalized patients were also collected by consultation of clinical documents. Results Cumulative incidence of Long COVID-19 resulted to be 24.3% in primary care patients and 58% in hospitalized patients. The most frequently reported symptoms were abnormal fatigue (7%), neurological (6.8%), and respiratory disorders (6%) for the primary care cohort. Hospitalized patients displayed more frequently psychological symptoms (36.7%), cardiac involvement (23.3%), and respiratory disorders (18.3%). No difference was observed in cumulative incidence in males and females in both cohorts. Previous diseases did not influence the probability to develop Long COVID-19. The prevalence of Long COVID-19 was 46.5% in children who were symptomatic during acute infection and 11.5% in asymptomatic ones. Children aged 0 to 5 years had a greater risk to develop respiratory symptoms, while adolescents (aged 11–16 years) had a greater risk to develop neurological and psychological Long COVID-19 symptoms. Conclusions Our study demonstrates that Long COVID-19 is a reality in pediatric age and could involve even patients with mild or no acute symptoms. The results stress the importance of monitoring primary care pediatric patients after acute COVID-19 infection and the relevance of vaccination programs in pediatric population, also in order to avoid the consequences of Long COVID-19 syndrome.

Recent studies identified pregnancy as a high-risk condition for the development of maternal-fetal complications in the case of the SARS-CoV-2 infection. Therefore, the scientific community is now considering pregnant women a “fragile” category that should be vaccinated with high priority. The number of pregnant women undergoing hospitalization since summer 2021, including Intensive Care Unit admission, is growing, as well as the risk of preterm birth. Evidence from both animals and humans suggest that, similarly to other vaccines routinely administered in pregnancy, COVID-19 vaccines are not crossing the placenta, do not increase the risk of miscarriage, preterm birth, stillbirth, the birth of small gestational age neonates, as well as the risk of congenital abnormalities. To date, the World Health Organization and scientific literature are promoting and encouraging the vaccination of all pregnant and lactating women. The aim of our narrative review is to present the available literature regarding this issue with the aim to provide appropriate answers to the most frequent requests, doubts, and fears that have led many expecting and lactating women not to become vaccinated during this pandemic period.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder evolving over the lifetime of individuals. The oral and gut microbial ecosystems are closely connected to each other and the brain and are potentially involved in neurodevelopmental diseases. This narrative review aims to identify all the available evidence emerging from observational studies focused on the role of the oral microbiome in ASD. A literature search was conducted using PubMed and the Cochrane Library for relevant studies published over the last ten years. Overall, in autistic children, the oral microbiota is marked by the abundance of several microbial species belonging to the Proteobacteria phylum and by the depletion of species belonging to the Bacteroidetes phylum. In mouse models, the oral microbiota is marked by the abundance of the Bacteroidetes phylum. Oral dysbiosis in ASD induces changes in the human metabolome, with the overexpression of metabolites closely related to the pathogenesis of ASD, such as acetate, propionate, and indoles, together with the underexpression of butyrate, confirming the central role of tryptophan metabolism. The analysis of the literature evidences the close relationship between oral dysbiosis and autistic core symptoms; the rebuilding of the oral and gut ecosystems by probiotics may significantly contribute to mitigating the severity of ASD symptoms.

Necrotizing enterocolitis (NEC) represents the most common and lethal acute gastrointestinal emergency of newborns, mainly affecting those born prematurely. It can lead to severe long-term sequelae and the mortality rate is approximately 25%. Furthermore, the diagnosis is difficult, especially in the early stages, due to multifactorial pathogenesis and complex clinical pictures with mild and non-specific symptoms. In addition, the existing tests have poor diagnostic value. Thus, the scientific community has been focusing its attention on the identification of non-invasive biomarkers capable of prediction, early diagnosis and discriminating NEC from other intestinal diseases in order to intervene early and block the progression of the pathology. In this regard, the use of “omics” technologies, especially metabolomics and microbiomics, could be a fundamental synergistic strategy to study the pathophysiology of NEC. In addition, a deeper knowledge of the microbiota–host cross-talk can clarify the metabolic pathways potentially involved in the pathology, allowing for the identification of specific biomarkers. In this article, the authors analyze the state-of-the-art concerning the application of metabolomics and microbiota analysis to investigate this pathology and discuss the future possibility of the metabolomic fingerprint of patients for diagnostic purposes.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease typical of preterm infants. It is associated with high morbidity and risk of short- and long-term mortality. Despite improvements in perinatal care, its incidence has remained relatively constant: it occurs in 40-45% of infants born before the 29th week of gestation. Current definitions of this disease show several limitations, and this could be linked, in particular, to its multifactorial pathogenesis. Today, BPD occurs more commonly in extremely preterm infants, and it is characterized by a milder but longer course, mainly due to the extreme immaturity of the lungs at birth, with arrested maturation in the canalicular or early saccular stage, interruption of alveolarization, altered and dysregulated microvascular development, high pulmonary vascular resistance, and abnormal vascular reactivity. The pathogenesis of BPD is multifactorial: prolonged exposure to high oxygen levels, the lung damage caused by mechanical ventilation, the inflammatory state and, last but not least, the epigenetic/genetic risk factors. Further investigations concerning BPD pathogenesis showed that extremely preterm birth is associated with significative dysbiosis in airway microbiome. In the future, metabolomics, thanks to its ability to identify instant variations of metabolites possibly related to disorders, could help to recognize those associated with BPD and its pathways alterations.

During the Symposium “Systems Medicine. Integration models in clinical practice and new therapeutic solutions”, "The Milan Declaration 2022 – New goals for Medicine" – which outlines the current and future social and health scenarios that make necessary to define a new paradigm of Medicine – was approved by the speakers (Prof. Giuseppe Bellelli, Prof. Sergio Bernasconi, Prof. Gianni Bona, Prof. Mario Clerici, Prof. Giuseppe De Benedittis, Dr. Marco Del Prete, Prof. Fabio Esposito, Prof. Vassilios Fanos, Prof. Alessandro Genazzani, Prof. Paolo Inghilleri, Prof. Davide Lauro, Prof. Jeanette Maier, Prof. Stefano Masiero, Prof. Marco Matucci Cerinic, Prof. Alberto Migliore, Prof. Emilio Minelli, Prof. Andrea Modesti, Prof. Claudio Molinari, Prof. Valter Santilli, Prof. Umberto Solimene). The Symposium was held in Milan, Italy, at the University of Milan, on 5 May 2022 under the auspices of: World Health Organization (WHO) Collaborating Center for Integrative Medicine, P.R.M. Academy (International Academy of Physiological Regulating Medicine), FEMTEC (Worldwide Federation of Hydrotherapy and Climatotherapy), under the patronage of: Italian Ministry of Health, FNOMCeO (Italian Federation of the Associations of Surgeons and Dentists).

Gestational diabetes mellitus (GDM), or any degree of glucose intolerance recognized for the first time during pregnancy, is one of the diseases that most frequently aggravates the course of gestation. Missed or late diagnosis and inadequate treatment are associated with high maternal and fetal morbidity, with possible short- and long-term repercussions. Estimates on the prevalence of GDM are alarming and increasing by about 30% in the last 10–20 years. In addition, there is the negative influence of the SARS-CoV-2 emergency on the glycemic control of pregnant women, making the matter increasingly topical. To date, knowledge on the metabolic maturation of newborns is still incomplete. However, in light of the considerable progress of the theory of “developmental origins of health and disease,” the relevant role of the intrauterine environment cannot be overlooked. In fact, due to the high plasticity of the early stages of development, some detrimental metabolic alterations during fetal growth, including maternal hyperglycemia, are associated with a higher incidence of chronic diseases in adult life. In this context, metabolomic analysis which allows to obtain a detailed phenotypic portrait through the dynamic detection of all metabolites in cells, tissues and different biological fluids could be very useful for the early diagnosis and prevention of complications. Indeed, if the diagnostic timing is optimized through the identification of specific metabolites, the detailed understanding of the altered metabolic pathway could also allow better management and more careful monitoring, also from a nutritional profile, of the more fragile children. In this context, a further contribution derives from the analysis of the intestinal microbiota, the main responsible for the fecal metabolome, given its alteration in pregnancies complicated by GDM and the possibility of transmission to offspring. The purpose of this review is to analyze the available data regarding the alterations in the metabolomic profile and microbiota of the offspring of mothers with GDM in order to highlight future prospects for reducing GDM-related complications in children of mothers affected by this disorder.

The alarming onset of some cases of myocarditis and pericarditis following the administration of Pfizer–BioNTech and Moderna COVID-19 mRNA-based vaccines in adolescent males has recently been highlighted. All occurred after the second dose of the vaccine. Fortunately, none of patients were critically ill and each was discharged home. Owing to the possible link between these cases and vaccine administration, the US and European health regulators decided to continue to investigate the potential causal relationship between COVID-19 mRNA vaccines and myocarditis. In any case, none of the patients fulfilled the criteria for multi-system inflammatory syndrome or Kawasaki-like disease and there was no evidence of acute SARS-CoV-2 infection.

Otorhinolaryngology (Ear, Nose and Throat-ENT) focuses on inflammatory, immunological, infectious, and neoplastic disorders of the head and neck and on their medical and surgical therapy. The fields of interest of this discipline are the ear, the nose and its paranasal sinuses, the oral cavity, the pharynx, the larynx, and the neck. Besides surgery, there are many other diagnostic aspects of ENT such as audiology and Vestibology, laryngology, phoniatrics, and rhinology. A new advanced technology, named metabolomics, is significantly impacting the field of ENT. All the “omics” sciences, such as genomics, transcriptomics, and proteomics, converge at the level of metabolomics, which is considered the integration of all “omics.” Its application will change the way several of ENT disorders are diagnosed and treated. This review highlights the power of metabolomics, including its pitfalls and promise, and several of its most relevant applications in ENT to provide a basic understanding of the metabolites associated with these districts. In particular, the attention has been focused on different heterogeneous diseases, from head and neck cancer to allergic rhinitis, hearing loss, obstructive sleep apnea, noise trauma, sinusitis, and Meniere’s disease. In conclusion, metabolomics study indicates a “fil rouge” that links these pathologies to improve three aspects of patient care: diagnostics, prognostics, and therapeutics, which in one word is defined as precision medicine.

The COVID-19 pandemic has led to an unprecedented closure of schools in terms of duration. The option of school closure, SARS-CoV-2 initially being poorly known, was influenced by the epidemiological aspects of the influenza virus. However, school closure is still under debate and seems unsupported by sure evidence of efficacy in the COVID-19 era. The aim of our narrative review is to discuss the available literature on SARS-CoV-2 spread among children and adolescents, in the school setting, trying to explain why children appear less susceptible to severe disease and less involved in viral spreading. We also tried to define the efficacy of school closure, through an overview of the effects of the choices made by the various countries, trying to identify which preventive measures could be effective for a safe reopening. Finally, we focused on the psychological aspects of such a prolonged closure for children and adolescents. SARS-CoV-2, children, COVID-19, influenza, and school were used as key words in our literature research, updated to 29 March 2021. To our knowledge, this is the first review summarizing the whole current knowledge on SARS-CoV-2 spreading among children and adolescents in the school setting, providing a worldwide overview in such a pandemic context.

Abstract Background In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. Methods Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. Results The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. Conclusions We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research.

Even today, tuberculosis in childhood is a disease that is often undiagnosed and undertreated. In the absence of therapy with antituberculosis drugs, children in the first years of life have a high degree of severe forms and mortality. In these children, symptoms are often not very specific and can easily be confused with other diseases of bacterial, viral or fungal etiology, making diagnosis more difficult. Nevertheless, the introduction of new diagnostic techniques has allowed a more rapid identification of the infection. Indeed, Interferon gamma release assay (IGRA) is preferred to the Mantoux, albeit with obvious limitations in children aged

Abstract Children with medical complexity represent a big challenge for the physicians, their families and the society as well. Although there is no clear definition of this type of patients, they are affected by a chronic, often very severe condition for their whole life. They also represent a huge cost for the health care system due to their needs of continuous assistance. In this review we summarized the definitions of child with medical complexity. Then we illustrated the strategies to treat and take care of these children in order to look at them not as a burden or a cost but as an opportunity to growth and improve as clinicians and to improve the society, to give them the best life they can live. We also wanted to give voice to the physicians, the parents and the children themselves to really show and understand what are their experiences and their feelings in dealing with their conditions. We concluded with the description of one example of children with medical complexity: prematurity. We discussed the progresses in their treatment so far in order to illustrate what is the future of pediatrics. Since it has been more and more acknowledged that every child with medical complexity is unique, the future of pediatric is to organize an individualized approach and to “see things with the eye of a child”.

Abstract Here we present the Authors’ answer to the Letter written by Dr. Garazzino and Colleagues with reference to our article “Long COVID-19 in children: an Italian cohort study”.

Abstract Background Necrotizing enterocolitis (NEC) and supraventricular tachycardia (SVT) are serious emergencies in the neonatal period. Although these conditions are recognized as distinct pathologies, literature reports suggest that recurrent episodes of SVT may predispose patients to NEC via disturbances in mesenteric blood flow and a decrease in tissue perfusion. Case presentation We present a case of a preterm infant affected by recurrent episodes of SVT who developed the initial stage of NEC on the 17th day of life. Moreover, a detailed description of all the cases described in the literature is reported. Materials and methods An integrative review of the updated literature in the Medline database and PubMed and scientific books and articles was conducted. The research from October 2019 to December 2019 was searched for with MeSH and free terms (necrotizing enterocolitis, supraventricular tachycardia) and was linked by Boolean operators. Conclusions SVT can be considered a risk factor for the development of NEC. Therefore, clinicians should have a high level of suspicion for NEC in infants affected by SVT. This article is the first structured literature review analysing the association between SVT and NEC.

Abstract In the last years, ‘omics’ technologies, and especially metabolomics, emerged as expanding scientific disciplines and promising technologies in the characterization of several pathophysiological processes. In detail, metabolomics, able to detect in a dynamic way the whole set of molecules of low molecular weight in cells, tissues, organs, and biological fluids, can provide a detailed phenotypic portray, representing a metabolic “snapshot.” Thanks to its numerous strength points, metabolomics could become a fundamental tool in human health, allowing the exact evaluation of individual metabolic responses to pathophysiological stimuli including drugs, environmental changes, lifestyle, a great number of diseases and other epigenetics factors. Moreover, if current metabolomics data will be confirmed on larger samples, such technology could become useful in the early diagnosis of diseases, maybe even before the clinical onset, allowing a clinical monitoring of disease progression and helping in performing the best therapeutic approach, potentially predicting the therapy response and avoiding overtreatments. Moreover, the application of metabolomics in nutrition could provide significant information on the best nutrition regimen, optimal infantile growth and even in the characterization and improvement of commercial products’ composition. These are only some of the fields in which metabolomics was applied, in the perspective of a precision-based, personalized care of human health. In this review, we discuss the available literature on such topic and provide some evidence regarding clinical application of metabolomics in heart diseases, auditory disturbance, nephrouropathies, adult and pediatric cancer, obstetrics, perinatal conditions like asphyxia, neonatal nutrition, neonatal sepsis and even some neuropsychiatric disorders, including autism. Our research group has been interested in metabolomics since several years, performing a wide spectrum of experimental and clinical studies, including the first metabolomics analysis of human breast milk. In the future, it is reasonable to predict that the current knowledge could be applied in daily clinical practice, and that sensible metabolomics biomarkers could be easily detected through cheap and accurate sticks, evaluating biofluids at the patient’s bed, improving diagnosis, management and prognosis of sick patients and allowing a personalized medicine. A dream? May be I am a dreamer, but I am not the only one.

The integrity of the gastrointestinal tract structure and function is seriously compromised by two pathological conditions sharing, at least in part, several pathogenetic mechanisms: inflammatory bowel diseases (IBD) and coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IBD and COVID-19 are marked by gut inflammation, intestinal barrier breakdown, resulting in mucosal hyperpermeability, gut bacterial overgrowth, and dysbiosis together with perturbations in microbial and human metabolic pathways originating changes in the blood and fecal metabolome. This review compared the most relevant metabolic and microbial alterations reported from the literature in patients with IBD with those in patients with COVID-19. In both diseases, gut dysbiosis is marked by the prevalence of pro-inflammatory bacterial species and the shortfall of anti-inflammatory species; most studies reported the decrease in Firmicutes, with a specific decrease in obligately anaerobic producers short-chain fatty acids (SCFAs), such as Faecalibacterium prausnitzii. In addition, Escherichia coli overgrowth has been observed in IBD and COVID-19, while Akkermansia muciniphila is depleted in IBD and overexpressed in COVID-19. In patients with COVID-19, gut dysbiosis continues after the clearance of the viral RNA from the upper respiratory tract and the resolution of clinical symptoms. Finally, we presented and discussed the impact of gut dysbiosis, inflammation, oxidative stress, and increased energy demand on metabolic pathways involving key metabolites, such as tryptophan, phenylalanine, histidine, glutamine, succinate, citrate, and lipids.

The effectiveness of SARS-CoV-2 vaccines is currently undermined by the rapid spread of variants of concern affecting an increasing number of people worldwide. Thus, new vaccine candidates are required to limit new waves of infections. On the one hand, the development of personalized vaccines, both on a personal and population level, may overcome the inter-individual heterogeneity in vaccine-induced immune responses and in adverse side effects. On the other hand, the development of a universal coronaviruses vaccine broadly protective against all betacoronaviruses may overcome the coronaviruses genetic polymorphism due to the generation of new genomes and homologous genetic recombination in multiple species. The preparation of a tailored and universal vaccine, that is an “ideal” vaccine, could be realized with the contribution of the system biology approach and, in particular, of metabolomics, in conjunction with a global policy strategy and adequate public governance.

The growing obesity epidemic in childhood is increasingly concerning for the related physical and psychological consequences, with a significant impact on health care costs in both the short and the long term. Nonetheless, the scientific community has not yet completely clarified the complex metabolic mechanisms underlying body weight alterations. In only a small percentage of cases, obesity is the result of endocrine, monogenic, or syndromic causes, while in much more cases, lifestyle plays a crucial role in obesity development. In this context, the pediatric age appears to be of considerable importance as prevention strategies together with early intervention can represent important therapeutic tools not only to counteract the comorbidities that increasingly affect children but also to hinder the persistence of obesity in adulthood. Although evidence in the literature supporting the alteration of the microbiota as a critical factor in the etiology of obesity is abundant, it is not yet fully defined and understood. However, increasingly clear evidence is emerging regarding the existence of differentiated metabolic profiles in obese children, with characteristic metabolites. The identification of specific pathology-related biomarkers and the elucidation of the altered metabolic pathways would therefore be desirable in order to clarify aspects that are still poorly understood, such as the consequences of the interaction between the host, the diet, and the microbiota. In fact, metabolomics can characterize the biological behavior of a specific individual in response to external stimuli, offering not only an eventual effective screening and prevention strategy but also the possibility of evaluating adherence and response to dietary intervention.

The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are not covered in newborn screening and the diagnostic profiling in the metabolic laboratory is indispensable to reach a correct diagnosis. In recent years, Metabolomics helped to obtain a better understanding of pathogenesis and pathophysiology of IEMs, by validating diagnostic biomarkers, discovering new specific metabolic patterns and new IEMs itself. The expansion of Metabolomics in clinical biochemistry and laboratory medicine has brought these approaches in clinical practice as part of newborn screenings, as an exam for differential diagnosis between IEMs, and evaluation of metabolites in follow up as markers of severity or therapies efficacy. Lastly, several research groups are trying to profile metabolomics data in platforms to have a holistic vision of the metabolic, proteomic and genomic pathways of every single patient. In 2018 this team has made a review of literature to understand the value of Metabolomics in IEMs. Our review offers an update on use and perspectives of metabolomics in IEMs, with an overview of the studies available from 2018 to 2022.

In this paper, we describe the history of the 17 International Workshops on Neonatology and Pediatrics held in Cagliari, Italy, which saw the overall presence of about 11,500 participants. Some of the world’s most renowned specialists from more than 60 countries have been present in Cagliari in these years. They have created a network of scientific and human relations that have changed, improved and enriched us all. In 2019 the meeting was followed by the 40th Congress of the Union of Middle-Eastern and Mediterranean Pediatric Societies (UMEMPS), founded 60 years ago. In 2020, due to the COVID-19 pandemic, the meeting was virtual. Also this year, the meeting will be virtual. The title of this year’s Workshop, “The future is now”, underscores the trajectory that assistance, research and teaching will follow in the coming years, in an integrated way with Adult Medicine, taking into account what happened or is still going to happen. These advances are strictly related to children’s future, to their health in terms of new therapies and prevention.

ABSTRACT Necrotizing enterocolitis (NEC) is among the most relevant gastrointestinal diseases affecting mostly prematurely born infants with low birth weight. While intestinal dysbiosis has been proposed as one of the possible factors involved in NEC pathogenesis, the role of the gut microbiota remains poorly understood. In this study, the gut microbiota of preterm infants was explored to highlight differences in the composition between infants affected by NEC and infants prior to NEC development. A large-scale gut microbiome analysis was performed, including 47 shotgun sequencing data sets generated in the framework of this study, along with 124 retrieved from publicly available repositories. Meta-analysis led to the identification of preterm community state types (PT-CSTs), which recur in healthy controls and NEC infants. Such analyses revealed an overgrowth of a range of opportunistic microbial species accompanying the loss of gut microbial biodiversity in NEC subjects. Moreover, longitudinal insights into preterm infants prior to NEC development indicated Clostridium neonatale and Clostridium perfringens species as potential biomarkers for predictive early diagnosis of this disease. Furthermore, functional investigation of the enzymatic reaction profiles associated with pre-NEC condition suggested DL-lactate as a putative metabolic biomarker for early detection of NEC onset. IMPORTANCE Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease occurring predominantly in premature infants whose etiology is still not fully understood. In this study, the analysis of infant fecal samples through shotgun metagenomics approaches revealed a marked reduction of the intestinal (bio)diversity and an overgrowth of (opportunistic) pathogens associated with the NEC development. In particular, dissection of the infant’s gut microbiome before NEC diagnosis highlighted the potential involvement of Clostridium genus members in the progression of NEC. Remarkably, our analyses highlighted a gastrointestinal DL-lactate accumulation among NEC patients that might represent a novel potential functional biomarker for the early diagnosis of NEC.

Metabolomics is a promising tool for studying exercise physiology and exercise-associated metabolism. It has recently been defined with the term “sportomics” due to metabolomics’ capability to characterize several metabolites in several biological samples simultaneously. This narrative review on exercise metabolomics provides an initial and brief overview of the different metabolomics technologies, sample collection, and further processing steps employed for sport. It also discusses the data analysis and its biological interpretation. Thus, we do not cover sample collection, preparation, and analysis paragraphs in detail here but outline a general outlook to help the reader to understand the metabolomics studies conducted in team-sports athletes, alongside endeavoring to recognize existing or emergent trends and deal with upcoming directions in the field of exercise metabolomics in a team-sports setting.

Objective: To investigate changes in the urine metabolome of very low birth weight preterm newborns with necrotizing enterocolitis (NEC) and feed intolerance, we conducted a longitudinal study over the first 2 months of life. The metabolome of NEC newborns was compared with two control groups that did not develop NEC: the first one included preterm babies with feed intolerance, while the second one preterm babies with good feed tolerance.Methods: Newborns developing NEC within the 3 weeks of life were identified as early onset NEC, while the remaining as late onset NEC. Case-control matching was done according to the gestational age (±1 week), birth weight (± 200 g), and postnatal age. A total of 96 urine samples were collected and analyzed. In newborns with NEC, samples were collected before, during and after the diagnosis over the first 2 months of life, while in controls samples were collected as close as possible to the postnatal age of newborns with NEC. Proton nuclear magnetic resonance (1H NMR) spectroscopy was used for metabolomic analysis. Data were analyzed by univariate and multivariate statistical analysis.Results: In all the preterm newborns, urine levels of betaine, glycine, succinate, and citrate positively correlated with postnatal age. Suberate and lactate correlated with postnatal age in preterms with NEC and in controls with food intolerance, while N,N-dimethylglycine (N,N-DMG) correlated only in controls with good digestive tolerance. Preterm controls with feed intolerance showed a progressive significant decrease of N-methylnicotinamide and carnitine. Lactate, betaine, myo-inositol, urea, creatinine, and N,N-dimethylglycine discriminated late-onset NEC from controls with good feed tolerance.Conclusion: Our findings are discussed in terms of contributions from nutritional and clinical managements of patients and gut microbiota.

The aim of this work is to investigate 7 secrets of COVID-19 (fever, ACE2 receptors, gut-lung axis, metabolomics, microbiomics, probiotics, diet), hoping to reveal a small part of some of these and to increase anyhow the knowledge on SARS-CoV-2 and its weaknesses to be able to defeat it. In particular, in the opinion of the authors, significant improvements in contrasting the Coronavirus, and the pandemics that will follow, could derive from the use of “omics” disciplines, namely metabolomics (the stethoscope of the future) and microbiomics (an unrecognized player). The discovery of new biomarkers using metabolomics could be used in clinical practice as predictive diagnostic tools or to evaluate the effectiveness and toxicity of a drug, in order to be able to provide the patient with a personalized, tailor-made medicine: precision medicine. Our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our understanding of viral infection, and create new ways in which we might treat and prevent it. We strongly believe that the 3 M’s (Metabolomics, Microbiomics and Machine learning [Artificial Intelligence]) will be the right route to the future for risk assessment, early diagnosis, patient management and decision-making. By now, probiotics could help, fighting face to face against the virus. Moreover, the diet may be a key driver in determining the severity of COVID-19 and further studies are needed to explore the secret language between diet, bacteria, viruses and metabolites in determining individualized susceptibility or resilience to COVID-19.

Variation in metabolite levels reflects individual differences in genetic and environmental factors. Here, we investigated the role of these factors in urinary metabolomics data in children. We examined the effects of sex and age on 86 metabolites, as measured on three metabolomics platforms that target amines, organic acids, and steroid hormones. Next, we estimated their heritability in a twin cohort of 1300 twins (age range: 5.7–12.9 years). We observed associations between age and 50 metabolites and between sex and 21 metabolites. The monozygotic (MZ) and dizygotic (DZ) correlations for the urinary metabolites indicated a role for non-additive genetic factors for 50 amines, 13 organic acids, and 6 steroids. The average broad-sense heritability for these amines, organic acids, and steroids was 0.49 (range: 0.25–0.64), 0.50 (range: 0.33–0.62), and 0.64 (range: 0.43–0.81), respectively. For 6 amines, 7 organic acids, and 4 steroids the twin correlations indicated a role for shared environmental factors and the average narrow-sense heritability was 0.50 (range: 0.37–0.68), 0.50 (range; 0.23–0.61), and 0.47 (range: 0.32–0.70) for these amines, organic acids, and steroids. We conclude that urinary metabolites in children have substantial heritability, with similar estimates for amines and organic acids, and higher estimates for steroid hormones.

Introduction: In premature neonates, the persistence of hemodynamically significant ductus arteriosus (hsPDA) can be associated with short- and long-term consequences, impairing their outcome. The correct strategy of management for such condition is under debate, especially regarding contraindications and/or side effects. In recent years, metabolomics was applied to several perinatal, pediatric, and adult conditions to investigate potential biomarkers of disease, which have become useful for early diagnosis and/or therapeutic management.Aim of the Study: The main purpose of our exploratory study was to asses, through 1H-NMR metabolomics analysis of urinary samples at birth, possible metabolic pathways differentiating, with a significant predictive power, those preterm neonates who will subsequently develop hsPDA and neonates of comparable gestational age (GA) who will undergo spontaneous ductal closure or the persistence of an irrelevant PDA (no-hsPDA). Moreover, we investigated potential prenatal or perinatal clinical factors potentially influencing the development of hsPDA.Materials and Methods: We enrolled n = 35 preterm neonates with GA between 24 and 32 weeks; urinary samples were collected within the first 12 h of life. Patients were closely monitored regarding intensive care, respiratory support, fluid balance and administered drugs; an echocardiogram was performed at 48–72 h.Results: Our results reported a significant correlation between lower GA at birth and the development of hsPDA. Moreover, neonates with GA ≤ 30w developing hsPDA were characterized by lower Apgar scores at 1′ and 5′, higher rates of perinatal asphyxia, higher need of delivery room resuscitation and subsequent surfactant administration. Interestingly, metabolomics analysis at birth detected a clear separation between the 1H-NMR urinary spectra of subjects GA ≤ 30w not developing hsPDA (n = 19) and those of subjects born at GA ≤ 30w in which hsPDA was confirmed at 48–72 h of life (n = 5).Conclusions: This is the first study applying metabolomics to investigate the PDA condition. Although preliminary and conducted on a limited sample, our results reveal that metabolomics could be a promising tool in the early identification of hsPDA, potentially superior to the clinical or laboratory predictive tools explored to date and even to the clinical observations and correlations in our sample, through the detection of specific urinary metabolites.

Docosahexaenoic acid (DHA) is an essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) and represents the dominant structural fatty acid in the retina and in the brain's gray matter. Due to its active participation in the development of the nervous system, DHA is one of the most studied LCPUFA and is currently considered a critical nutrient during pregnancy and breastfeeding. Increasing evidence in literature suggests that an adequate concentration of DHA is required from the fetal stage through to early life to ensure optimal neurological development. Likewise, many studies in literature demonstrated that an adequate supply of DHA during pregnancy and lactation is essential to promote proper brain development in utero and in early life. Daily supplementation of DHA in newborns has potentially stronger effects compared to maternal supplementation during pregnancy. Supplementation initiated in the second year of life in children born preterm did not result in global cognitive development improvements. Preliminary findings arising from metabolomics has reported that mother's milk and infant formula supplementation of Vitamin D associated with DHA results in a higher antioxidant and protective action, with a possible positive influence on renal function and body fat on preterm infants compared to those receiving only vitamin D. Recent applications of metabolomic studies on newborns may lead to a better understanding of the metabolic process linked to early nutrition and, subsequently, to the development of targeted and personalized nutritional strategies.

All newborns should be examined for ocular structural abnormalities, an essential part of the newborn assessment. Early detection of congenital ocular disorders is important to begin appropriate medical or surgical therapy and to prevent visual problems and blindness, which could deeply affect a child’s life. The present review aims to describe the main congenital ocular anomalies in newborns and provide images in order to help the physician in current clinical practice.

Pre-pregnancy body mass index (BMI) is a major relevance factor, since maternal overweight and obesity can impair the pregnancy outcome and represent risk factors for several neonatal, childhood, and adult conditions, including excessive weight gain, cardiovascular disease, diabetes mellitus, and even behavioral disorders. Currently, breast milk (BM) composition in such category of mothers was not completely defined. In this field, metabolomics represents the ideal technology, able to detect the whole profile of low molecular weight molecules in BM. Limited information is available on human BM metabolites differences in overweight or obese compared to lean mothers. Analyzing all the metabolomics studies published on Medline in English language, this review evaluated the effects that 8 specific types of metabolites found altered by maternal overweight and obesity (nucleotide derivatives, 5-methylthioadenosine, sugar-alcohols, acylcarnitine and amino acids, polyamines, mono-and oligosaccharides, lipids) can exert on the risk of offspring obesity development and other potentially associated health outcomes and complications. However, metabolites variations in samples collected from overweight and obese mothers and the potentially correlated effects highlighted below still need further investigations and should be confirmed in future metabolomics studies on larger samples. Finally, the positive or negative influence of maternal overweight and obesity on the offspring, potentially exerted by breastfeeding, should be analyzed in close correlation with maternal age, genetic and environmental factors, including diet, and taking into account the interactions occurring between BM metabolites and lactobiome. The evaluation of all the factors affecting BM metabolites in overweight and obese mothers can lead to the comprehensive description of such biofluid and the related effects on breastfed subjects, potentially highlighting personalized needs of BM supplementation or short- and long-term prevention strategies to optimize offspring health.

The ongoing pandemic is the result of the spread of a recently identified Coronavirus, named SARS-CoV-2 (Severe Acute Respiratory Syndrome – Coronavirus – 2). Since 31th December 2019, when the first cluster was reported in Wuhan (China), the global Novel COronaVIrus Disease 2019 (COVID-19) cases significantly increased, and on 12th March 2020, the WHO Director declared the disease as pandemic. As of April 28th 2020, 2.982,688 cases and 210,193 deaths were reported globally. The aim of this article is the analysis of the main epidemiological characteristics of the current pandemic: transmission, basic reproduction number (R0), incubation period, global, European and Italian confirmed cases and deaths, focusing on the paediatric population.

Healthy lungs are not sterile. In the last decade, it was demonstrated that the healthy lung has its specific microbiota. It is much smaller in numerical terms, compared to the gut microbiota, but it is a unique microbiota that can affect the health and the diseases. With an estimated number of 10-100 bacteria for 1.000 human cells, the lower respiratory tract is one of the less populated surfaces by the bacteria of the whole human body. Even human fetal lungs host a “signature” of the microbiota. The composition of the lung microbiota depends on several factors, including the so-called “microbial immigration” from micro-aspiration and inhalation of microorganisms.The connection between the lung and the gastrointestinal tract is not entirely understood. Patients with respiratory infections generally have gut dysfunctions complications, which are related to a more severe clinical course, thus indicating gut-lung crosstalk. In this review we analyse the lung microbiota in newborns, infants and adults with respiratory disease. In acute pulmonary diseases such as sepsis, trauma, and acute respiratory distress syndrome (ARDS), the lung microbiota becomes rich in gut bacteria, such as Bacteroidetes and Enterobacteriaceae. This phenomenon is also called “more gut in the lung”. In acute situations, the gut becomes hyper-permeable (leaky gut), and the bacteria can translocate through the colon wall and reach the lung affecting the inflammation, the infection, and the acute pulmonary damage. The increased gut permeability is associated with an increased alveolus-capillary hyper-permeability as well. There are tight correlations between the lung microbiota and the admission in intensive care. In particular, the modifications of the lung microbiota can help in predicting in which way the patients in critical condition will respond to the treatments. It has been investigated if the different incidence depending on age and the different courses between adults and children for Novel COronaVIrus Disease 2019 (COVID-19) could be due to the different concentrations and/or activation of angiotensin-converting enzyme 2 (ACE2) at the intestinal and pulmonary level. ACE2 is mainly localized on the luminal surface of the intestinal epithelial cells and it has been hypothesized that gut microbiota influences the action of ACE2. Thus, a close relationship between COVID-19 and the microbiota can be hypothesized (it has been studied in cats). Potential interventions for COVID-19 are: nutritional, antiviral, anti-coronavirus, and miscellanea. Other options could include also probiotics, especially Bifidobacteria and Lactobacilli, namely L. gasseri. In the next future, metabolomics could be applied in the study of COVID-19, deciphering the secret languages between viruses, bacteria and the organism.

Novel COronaVIrus Disease 2019 (COVID-19) is an emerging disease of public health concern because it is caused by a newly identified pathogen, against which humans have no pre-existing immunity. Since its outbreak, a growing number of studies have examined COVID-19 in adults, but the data on its epidemiological and clinical characteristics in newborns and in children are few and patchy. Children appear to develop moderate-mild or silent forms of the disease; to our knowledge, only two cases of death (a 14-year-old and a 16-year-old teenagers) have been reported. Arguably, the number of pediatric cases may be underestimated, since presumably cases with mild or no symptoms are not brought to the doctor’s attention. We have selected the most interesting and significant papers (including some pre-publication or ahead-of-print papers). The key factors in the pathophysiology of COVID-19, available data on pregnancy, the neonatal period, and later are discussed. A review of pediatric cases is available and 3 practical algorithms help the reader in clinical choices. Finally, diagnostic criteria and treatment are presented.

Biomarkers are of interest as potential diagnostic and predictive instruments in personalized medicine. We present the first urinary metabolomics biomarker study of childhood aggression. We aim to examine the association of urinary metabolites and neurotransmitter ratios involved in key metabolic and neurotransmitter pathways in a large cohort of twins (N = 1,347) and clinic-referred children (N = 183) with an average age of 9.7 years. This study is part of ACTION (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies), in which we developed a standardized protocol for large-scale collection of urine samples in children. Our analytical design consisted of three phases: a discovery phase in twins scoring low or high on aggression (N = 783); a replication phase in twin pairs discordant for aggression (N = 378); and a validation phase in clinical cases and matched twin controls (N = 367). In the discovery phase, 6 biomarkers were significantly associated with childhood aggression, of which the association of O-phosphoserine (β = 0.36; SE = 0.09; p = 0.004), and gamma-L-glutamyl-L-alanine (β = 0.32; SE = 0.09; p = 0.01) remained significant after multiple testing. Although non-significant, the directions of effect were congruent between the discovery and replication analyses for six biomarkers and two neurotransmitter ratios and the concentrations of 6 amines differed between low and high aggressive twins. In the validation analyses, the top biomarkers and neurotransmitter ratios, with congruent directions of effect, showed no significant associations with childhood aggression. We find suggestive evidence for associations of childhood aggression with metabolic dysregulation of neurotransmission, oxidative stress, and energy metabolism. Although replication is required, our findings provide starting points to investigate causal and pleiotropic effects of these dysregulations on childhood aggression.

Before birth, different organs retain hematopoiesis. The liver is involved in the 6th-8th week of gestation. The hepatic hematopoietic stem cell (HSC) niche begins when HSCs colonize the liver and make contact with sinusoidal endothelial cells. The aim of this study is to characterize the development of each hematopoietic cell lineage in 9 human liver specimens between 10 and 29 weeks of gestation with immunohistochemistry. Hematopoietic activity was coherent with gestational age. Erythropoiesis was the greatest fraction of fetal liver hematopoiesis: myeloid/erythroid ratio was inverted compared to the adult bone marrow. Myelopoiesis was compartmentalized in the periportal zone. Factor-VIII-positive cells were small, with a megakaryoblast-like morphology. Lymphoid precursors were absent. A small quantity of T and B lymphocytes was found. CD34-reactive hematopoietic stem and progenitor cells were found in a minority of cells. The understanding of the hematopoietic process during gestation could in the future contribute to better understand child and adult hematologic conditions.

Understanding the composition of human milk (HM) can provide important insights into the links between infant nutrition, health, and development. In the present work, we have longitudinally investigated the metabolome of milk from 36 women delivering preterm at different gestational ages (GA): extremely (1H NMR metabolic profiles of specimens in relation to the degree of prematurity and lactation stage. We observed a high impact of both the mother’s phenotype and lactation time on HM metabolome composition. Furthermore, statistically significant differences, although weak, were observed in terms of GA when comparing extremely and moderately preterm milk. Overall, our study provides new insights into preterm HM metabolome composition that may help to optimize feeding of preterm newborns, and thus improve the postnatal growth and later health outcomes of these fragile patients.