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(1) Objective: This systematic review summarizes current knowledges about maternal and neonatal outcomes following COVID-19 vaccination during pregnancy and breastfeeding. (2) Study design: PubMed, Cochrane Library, and the Education Resources Information Center (ERIC) were searched up to 27 October 2021. The primary outcome was to estimate how many pregnant and lactating women were reported to be vaccinated and had available maternal and neonatal outcomes. (3) Results: Forty-five studies sourcing data of 74,908 pregnant women and 5098 lactating women who received COVID-19 vaccination were considered as eligible. No major side-effects were reported, especially during the second and third trimester of pregnancy and during breastfeeding. Conversely, available studies revealed that infants received specific SARS-CoV-2 antibodies after maternal vaccination. (4) Conclusions: Vaccination against the SARS-CoV-2 virus should be recommended for pregnant women, after the pros and cons have been adequately explained. In particular, given the still limited evidence and considering that fever during the first months of gestation increases the possibility of congenital anomalies, they should be carefully counseled. The same considerations apply to breastfeeding women, also considering the immune responses that mRNA vaccines can generate in their human milk.

Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.

The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota \"core\" of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.

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

Small for gestational age (SGA) is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate the correlation of birthweight with the severity of liver damage in a large cohort of children with NAFLD. Two hundred and eighty-eight consecutive Caucasian Italian overweight/obese children with biopsy-proven NAFLD were included in the study. We examined the relative association of each histological feature of NAFLD with metabolic alterations, insulin-resistance, I148M polymorphism in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, and birthweight relative to gestational age. In the whole NAFLD cohort, 12.2% of patients were SGA, 62.8% appropriate for gestational age (AGA), and 25% large for gestational age (LGA). SGA children had a higher prevalence of severe steatosis (69%) and severe portal inflammation (14%) compared with the AGA and LGA groups. Notably, severe steatosis (>66%) was decreasing from SGA to AGA and LGA, whereas the prevalence of moderate steatosis (33-66%) was similar in three groups. The prevalence of type 1 NAFLD is higher in the LGA group with respect to the other two groups (25% vs.5.2% vs.9.4%), whereas the SGA group shows a higher prevalence of overlap type (85.8%) with respect to the LGA group (51.4%) but not compared with the AGA group (75%). At multivariable regression analysis, SGA at birth increased fourfold the likelihood of severe steatosis (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.43-10.9, P=0.008) and threefold the likelihood of NAFLD Activity Score (NAS)≥5 (OR 2.98, 95% CI 1.06-8.33, P=0.037) independently of homeostasis model assessment of insulin resistance and PNPLA3 genotype. The PNPLA3-CC wild-type genotype was the strongest independent predictor of the absence of significant fibrosis (OR 0.26, 95% CI 0.13-0.52, P=<0.001). In children with NAFLD, the risk of severe steatosis is increased by SGA at birth, independent of and in addition to other powerful risk factors (insulin-resistance and I148M variant of the PNPLA3 gene).

Sepsis remains the second cause of death among neonates after the pathological consequences of extreme prematurity. In this review we summarized knowledge about pathogens causing early-onset sepsis (EOS) and late-onset sepsis (LOS), the role of perinatal risk factors in determining the EOS risk, and the tools used to reduce unnecessary antibiotics. New molecular assays could improve the accuracy of standard blood cultures, providing the opportunity for a quick and sensitive tool. Different sepsis criteria and biomarkers are available to date, but further research is needed to guide the use of antibiotics according to these tools. Beyond the historical antibiotic regimens in EOS and LOS episodes, antibiotics should be based on the local flora and promptly modulated if specific pathogens are identified. The possibility of an antibiotic lock therapy for central venous catheters should be further investigated. In the near future, artificial intelligence could help us to personalize treatments and reduce the increasing trend of multidrug-resistant bacteria.

Diaphragmatic paralysis (DP) in neonates is a rare yet potentially life-threatening cause of respiratory distress, often resulting from obstetric trauma or cardiac surgery. This report presents two distinct cases of bilateral DP: one following a dystocic delivery with associated brachial plexus involvement, and the other linked to a genetic mutation (SYNGAP1) in a neonate with no birth trauma. Diagnosis was established through imaging, fluoroscopy, electromyography, and genetic testing. In both cases, conservative management was initially pursued; however, due to persistent respiratory failure, invasive interventions were required. The first patient underwent bilateral diaphragmatic plication with favorable outcomes, while the second required tracheostomy due to poor response to non-invasive ventilation with good outcome. These cases highlight the diagnostic and therapeutic challenges of neonatal DP, emphasizing the need for individualized treatment strategies in the absence of standardized guidelines. Early diagnosis and a multidisciplinary approach are crucial to optimize respiratory outcomes and reduce complications from prolonged mechanical ventilation.

Neonatal chylothorax is associated with high morbidity and mortality, partly due to increased infection risk from lymphocyte depletion and hypogammaglobulinemia. However, data specific to chylothorax cohorts are limited. This study aimed to investigate lymphocyte subsets and immunoglobulin levels in neonates with congenital and acquired chylothorax. We retrospectively enrolled 18 neonates with chylothorax admitted to our NICU between January 2023 and January 2025. Inclusion criteria were term or preterm infants with congenital or acquired chylothorax and paired peripheral blood and chyle samples collected within 48 hours of effusion onset. Lymphocyte subsets and immunoglobulin levels were compared between blood and chyle, and between congenital and acquired chylothorax. Chyle samples showed significantly higher leukocyte, lymphocyte (percentage and absolute), and T-cell counts compared to blood. Conversely, B lymphocyte percentages and Natural killer (NK) cell counts were significantly lower in chyle, as were IgG and IgM levels. Three patients (16.7%) had absolute lymphopenia, particularly within the T-cell and NK-cell subsets, and five (27.8%) had hypogammaglobulinemia. Fifteen infants (83.3%) developed late-onset sepsis, primarily bacterial, with some fungal cases. Absolute T-cell subset numbers in chyle were higher in acquired versus congenital chylothorax, while percentages and immunoglobulin levels were largely similar. Our findings confirm a specific pattern of immune dysregulation in neonates with chylothorax, with distinct lymphocyte and immunoglobulin profiles in chyle. In particular, the T-cell subsets were enriched in the chyle. A multicenter, prospective randomized trial is warranted to assess the utility of immunoglobulin therapy in infection prevention in this population.

Objective To review the clinical and molecular genetic characteristics of 16 patients presenting a suspected diagnosis of Kabuki syndrome (KS) in the first year of life, to evaluate the clinical handles leading to a prompt diagnosis of KS in newborns. Clinical diagnosis of KS can be challenging during the first year of life, as many diagnostic features become evident only in subsequent years. Methods All patients were clinically investigated by trained clinical geneticists. A literature review was performed using the Pubmed online database and diagnostic criteria suggested by DYSCERNE–Kabuki Syndrome Guidelines (2010) were used (a European Network of Centres of Expertise for Dysmorphology, funded by the European Commission Executive Agency for Health and Consumers (DG Sanco), Project 2006122). Molecular analysis of the known causative genes of KS, KMT2D/MLL2 and KDM6A, was performed through MiSeq-targeted sequencing platform. All mutations identified were validated by Sanger sequencing protocols. Results Mutations in KMT2D gene were identified in 10/16 (62%) of the patients, whereas none of the patients had KDM6A mutations. Facial dysmorphisms (94%), feeding difficulties (100%) and hypotonia (100%) suggested the clinical diagnosis of KS. No significative differences in terms of facial features were noticed between mutation positive and negative patients of the cohort. Brachydactyly, joint laxity and nail dysplasia were present in about 80% of the patients. Other congenital anomalies were most commonly present in the mutated group of patients, including left-sided cardiac abnormalities, skeletal, renal and anorectal malformations and hypertricosis. Conclusions We present an overview of patients with KS diagnosed during the first year of life. Early diagnosis is serviceable in terms of clinical management and for targeted genetic counselling.

Background Respiratory Syncytial Virus (RSV) is responsible for the majority of acute lower respiratory infections in infants and can affect also older age groups. Restrictions linked to the emergence of the SARS-CoV-2 pandemic and their subsequent lifting caused a change in the dynamics of RSV circulation. It is therefore fundamental to monitor RSV seasonal trends and to be able to predict its seasonal peak to be prepared to the next RSV epidemics. Methods We performed a retrospective descriptive study on laboratory-confirmed RSV infections from Bambino Gesù Children’s Hospital in Rome from 1st January 2018 to 31st December 2022. Data on RSV-positive respiratory samples ( n  = 3,536) and RSV-confirmed hospitalizations ( n  = 1,895) on patients aged 0–18 years were analyzed. In addition to this, a SARIMA (Seasonal AutoRegressive Integrated Moving Average) forecasting model was developed to predict the next peak of RSV. Results Findings show that, after the 2020 SARS-CoV-2 pandemic season, where RSV circulation was almost absent, RSV infections presented with an increased and anticipated peak compared to pre-pandemic seasons. While mostly targeting infants below 1 year of age, there was a proportional increase in RSV infections and hospitalizations in older age groups in the post-pandemic period. A forecasting model built using RSV weekly data from 2018 to 2022 predicted the RSV peaks of 2023, showing a reasonable level of accuracy (MAPE 33%). Additional analysis indicated that the peak of RSV cases is expected to be reached after 4–5 weeks from case doubling. Conclusion Our study provides epidemiological evidence on the dynamics of RSV circulation before and after the COVID-19 pandemic. Our findings highlight the potential of combining surveillance and forecasting to promote preparedness for the next RSV epidemics.