Italian Journal of Pediatrics最新文献

Background: Necrotizing enterocolitis (NEC) is a leading gastrointestinal condition in preterm infants, characterized by significant morbidity and mortality. Early recognition of risk factors is crucial for its prevention and prediction. This study focuses on identifying factors that contribute to the development of NEC in neonates.

Methods: A case-control study that looked back at 144 newborns hospitalized to a Wuhan hospital between January 2010 and March 2023 for NEC was carried out. Over the same period, another 144 children without NEC were identified and selected as the non-NEC group for comparison, following a 1:1 pairing ratio. The relevant data from these two groups of newborns were compared. Univariate analysis was conducted using T-tests or χ² tests, followed by multivariate logistic regression to determine independent risk factors and develop a clinical prediction model.

Results: A total of 288 neonates (144 NEC and 144 non-NEC) were enrolled. The independent risk variables for NEC, as shown by the multivariate logistic regression analysis (p < 0.05), were Small for Gestational Age (SGA), neonatal sepsis, neonatal hyperbilirubinemia, and non-human milk (HM) feeding. Furthermore, ROC (receiver operating characteristic) analysis showed that the AUC (area under the curve) of the Logistic regression model predicting the effect of neonatal necrotizing enterocolitis was 0.746, suggesting a high level of discriminative ability in differentiating efficacy. This model can be instrumental in facilitating early identification of infants prone to developing NEC in clinical settings.

Conclusion: In conclusion, the risk factors associated with newborn NEC include SGA, neonatal sepsis, and non-HM feeding. Newborn hyperbilirubinemia may potentially serve as a protective factor against NEC.

Background: Management of patients with steroid-sensitive nephrotic syndrome (SSNS) is challenging because of frequent relapses. Causal variants in the human leukocyte antigen (HLA) class II region that are associated with relapse remain undetermined.

Methods: We collected a cohort of East Asian individuals comprising 206 pediatric patients with SSNS and 435 healthy controls from Southwest China. Ninety children with steroid-sensitive nephrotic syndrome without relapse (SSNSWR) and 116 children with steroid-dependent and/or frequent relapse nephrotic syndrome (SDNS/FRNS) were genotyped using Sanger sequencing. We then measured the transcriptional level, allele expression imbalance (AEI) and functional proteins of HLA-DQA1 and HLA-DQB1 in different stages of SDNS/FRNS.

Results: rs1464545187 in ANKRD36 was associated with an approximately 1.69-fold greater risk for SSNSWR (P = 0.04; 95% confidence interval [CI], 1.05-2.72). Clustered risk variants in HLA-DQA1 and HLA-DQB1 were significantly associated with SDNS/FRNS (rs1047989: P = 2.26E-07, odds ratio [OR] = 2.25, 1.65-3.05; rs9273471: P = 5.45E-05, OR = 1.84, 1.37-2.46; HLA-DQB1*06:02: P = 0.017, OR = 0.19, 0.04-0.77). The genotype distributions of rs1047989, 2:171713702, rs1049123, rs9273471, and HLA-DQB1*06:02 in patients with SSNS were significantly different from those in healthy controls. rs1047989 (HLA-DQA1) was significantly associated with a greater number of infections at relapse in SDNS/FRNS patients (P = 0.045, OR = 6.79, 95% CI: 1.29-168.52). Flow cytometry showed that the proportion of cells expressing HLA-DQA1⁺/DQB1⁺ (HLA-DQA1⁺, P = 0.0046; HLA-DQB1⁺, P = 0.0045) was lowest in the relapse stage. In addition, the mRNA levels of HLA-DQA1 and HLA-DQB1 were significantly greater in the relapse group than in the remission group (HLA-DQA1, P = 0.03; HLA-DQB1, P = 0.002). No significant AEIs were detected in the different stages of SDNS/FRNS. The rs1047989 variant is likely to affect the structure and stability of HLA-DQA1.

Conclusion: rs1464545187 is a risk locus for SSNSWR but not SDNS/FRNS in Chinese children. Functional variations in HLA-DQA1 and HLA-DQB1 are implicated in regulating the immune response of SSNS patients, which may explain the typical triggering of SDNS/FRNS onset by infections.

Backgrounds: The incidence of Type 1 Diabetes (T1D) in children and adolescents is increasing by 3-4% per year. Children and adolescents with T1D (CwD) should receive person-centered, specialized treatment from a multidisciplinary team to ensure appropriate care. Italy is the first to implement a countrywide T1D screening program, which will raise the need for funding for specialized pediatric care. The study aims to update the organization of the Italian Centers for pediatric diabetes care.

Methods: In 2022, members of the 59 Italian Centers following CwD were invited to complete an email survey regarding the Centers' organization, characteristics, and activities. The questionnaire included information on responders, department organization, team composition, activities, and the organizational structures: department, ambulatory care services (AC), simple operational units (UOS), simple departmental operational units (UOSd), and complex operational units (UOC).

Results: The data collected referred to the year 2022. According to the results, 21,318 people with diabetes were treated. Of these, 19,643 subjects (92.1%) have T1D (16,672 were CwD), 387 (1,8%) have Type 2 Diabetes, and 1,288 (6,1%) have other forms of diabetes. Compared to the 2012 survey, a 13% decrease (from 68 to 59 Centers) in the number of pediatric Centers caring for CwD was observed with a parallel increase of total (+ 6.6%) and average (+ 22%) number of CwD per Center. The estimated prevalence of T1D has increased (1.4 vs. 1.7 per 1,000 CwD-2012 vs. 2022). A reduction in numbers for AC (-22%) and UOS (-35%) was observed, whereas UOSd/UOC increased by 50%. Almost 35% of the dietitians and 40% of the psychologists were not permanent members of the multidisciplinary diabetes team.

Conclusions: The observed decrease in the overall number of pediatric diabetes Centers, the reduction in specialized and dedicated HCPs, and the concurrent increase in the number of treated CwD in the last ten years indicate an alarming situation for pediatric diabetes treatment in Italy. Furthermore, the projected rise in CwD due to the National T1D screening program emphasizes the need for increased resources for specialized pediatric care of CwD at all stages.

Background: Home mechanical ventilation improves survival of critically ill children but partially affects quality of life. Studies in China have more often analyzed the risk factors for death from prolonged mechanical ventilation in hospitalized children while less attention has been paid to children with home mechanical ventilation. This study aimed to describe the quality of life of children with home mechanical ventilation and the influencing factors.

Methods: It was a prospective cohort study. The cohort population was children undergoing prolonged mechanical ventilation in the Pediatric Intensive Care Unit, with the outcome of whether they were alive or dead at 1-year follow-up after discharge. Standardized scores for quality of life were calculated using TNO-AZL Children's Health-Related Quality of Life and TNO-AZL Preschool Children Quality of Life. Multiple linear regression was used to analyze the factors affecting the quality of life.

Results: A total of 106 children were included, and 11 children (10.38%) died within one year after discharge. The mean age was 8.26 ± 4.10 years, and the hospitalization days was 68.46 ± 34.23. Child self-care had a significant effect on the risk of death one year after discharge, with higher Barthel self-care scores associated with a lower risk of death. There was a statistically significant difference in quality-of-life scores between the non-home and home mechanical ventilation groups, whereas tracheotomy or not had no effect. 81.57% of the surviving children with home mechanical ventilation were placed on invasive mechanical ventilation, with a mean ventilation duration of 19.94 h/d and a pressure-controlled mode primarily. Home invasive mechanical ventilation, age, and Barthel self-care score were independent influences on children's quality of life scores.

Conclusion: The long-term survival rate of children who transitioned to home mechanical ventilation in Shanghai, China, was higher than the international average. Most children were discharged to home invasive mechanical ventilation, decreasing their quality of life. It needs to continue standardizing the post-discharge management procedures and explore how to better transition to home non-invasive mechanical ventilation. It's necessary to describe the parents' quality of life with home mechanical ventilated children and its impact on child outcomes.

Background: The relationship between antenatal corticosteroids (ACS) and preterm infants born to mothers with hypertensive disorders of pregnancy (HDP) remains a subject of debate. To evaluate whether the use of ACS before delivery was associated with neonatal outcomes in very preterm infants born to mothers with HDP.

Methods: This multicenter cohort study enrolled all infants with gestational age at 24 to 31 week and admitted to tertiary NICUs of the Chinese Neonatal Network (CHNN) within 24 h of birth from 2019 to 2021. ACS administration was defined as at least one dose of dexamethasone or betamethasone before delivery. The primary outcome was surfactant and/ or invasive mechanical ventilation (IMV) within 72 h of life. Multivariable logistic regression analyses were performed to assess the association between ACS and neonatal outcomes.

Results: Among the 4,582 study infants born to mothers with HDP, 3,806 (83.1%) were exposed to ACS. ACS treatment was significantly associated with lower risk of requirement of surfactant and/ or IMV within 72 h of life (adjusted Odds Ratio = 0.60, 95% confidence interval 0.49-0.74). ACS exposure was also independently associated with decreased mortality, surfactant use, IMV, combined surfactant and IMV use and moderate or severe bronchopulmonary dysplasia. The severity of maternal HDP did not appear to influence the correlation between ACS treatment and neonatal outcomes. Our analysis also indicated that a single complete course seemed to have the most significant protective effect.

Conclusions: Our study reinforces the significant role of ACS in reducing severe respiratory morbidity and mortality in very preterm infants born to mothers with HDP.

Introduction: Neurodevelopmental disorders such as attention deficit and disruptive behaviour disorders (ADHD), autism spectrum disorder (ASD), and schizophrenia have been increasingly prevalent recently. Previous research has demonstrated that inflammatory activity from autoimmune diseases is involved in neurological diseases. However, some studies question the association between inflammatory activities and neurodevelopmental disorders. Herein, we attempt to clarify this relationship using Mendelian randomization (MR) analysis.

Methods: We used systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes mellitus (T1D) to represent autoimmune diseases. First, we conducted MR analysis to examine associated SNPs between autoimmune and neurodevelopmental disorders. Second, we performed bidirectional MR analysis to identify 429 types of signalling peptides and proteins or relevant receptors with causality reported diseases. Finally, we compared the genes with the gene loci identified in the available TWAS-hub site.

Results: The MR results of autoimmune diseases on neurodevelopmental disorders did not present any significant association in all models. However, we identified 20-45 factors in ADHD, ASD, and schizophrenia, including semaphorin 3, IL-27 receptor subunit alpha, and fibroblast growth factor 16, which were considered clinically significant pro-inflammatory mediators. GO and KEGG enrichment analyses revealed unequal integrities among the three neurodevelopmental diseases, and we failed to identify a shared pathway linking autoimmune diseases and neurodevelopmental disorders. TWAS analysis indicated that CHRNA5 potentially mediates inflammatory activities in schizophrenia.

Conclusion: According to our data, we failed to identify an association between autoimmune diseases and neurodevelopmental disorders. However, we demonstrated that some pro-inflammatory factors are involved in neurodevelopmental disorders.

Background: Infectious mononucleosis (IM) is a common disease in children; however, liver injury is its most common complication. However, the pathogenesis of IM complicated with liver injury is ambiguous. Thus, this study aimed to explore the potential mechanism of IM-associated liver injury.

Methods: This study was conducted at the Children's Hospital of Soochow University by collecting peripheral blood of 70 hospitalized children with IM. These patients were categorized into the liver injury (LIG, n = 35) and the non-liver injury groups (NLIG, n = 35), respectively. Subsequently, PBMCs and plasma were separated and obtained. PBMCs transcriptome sequencing was performed in two groups (5 cases in each group), and significantly differentially expressed genes (DEGs) were screened. Additionally, GO function enrichment, KEGG enrichment and GSEA analyses were performed. RT-PCR helped to detect the relative GBP5, NLRP3 and caspase-1 expressions in two groups (30 cases in each group) while the two groups' caspase-1, IL-1β and IL-18 in plasma levels were measured by ELISA. Thus, clinical and laboratory datas of 60 hospitalized children with IM were evaluated.

Results: Transcriptome sequencing results showed that 171 DEGs were screened in the NLIG group, compared with the LIG. Among them, 154 DEGs were up-regulated, and 17 were down-regulated, respectively. KEGG and GSEA analyses showed that IM-associated liver injury is correlated with a NOD-like receptor signaling pathway. Statistically significant differences were observed in the white blood cell and lymphocyte counts, CD3⁺CD4⁺ T cells, CD3⁺CD8⁺T cells, alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) of the two groups (p < 0.05). Compared with NLIG, GBP5, NLRP3 and caspase-1 expressions in PBMCs, as well as the caspase-1, IL-1β and IL-18 in plasma levels, were significantly higher in LIG (p < 0.001). A correlation analysis revealed a positive correlation of GBP5 with LDH, ALT, AST, CD3⁺CD8⁺T cells and NLRP3 (p < 0.05).

Conclusions: Our findings demonstrate that GBP5 contributes to liver injury in IM children through the NLRP3-dependent pathway.

Background: This study aimed to compare three different methods [breastfeeding, skin-to-skin contact (SSC), swaddling + holding] to reduce the pain felt by term newborns during a heel lance (HL).

Methods: This was a randomized three-group experimental study. The study sample included 90 newborns, 30 in each group. The data were collected using a pulse oximeter, a voice recorder, an Information Form, the Neonatal Infant Pain Scale (NIPS). The newborns' pain level, heart rate, and oxygen saturation were measured at three different times.

Results: No difference was found between the groups' mean NIPS scores before the HL procedure (p > 0.05). The mean NIPS scores 10 s after the procedure started and after the HL procedure were the lowest in the breastfeeding group, followed by the SSC and swaddling + holding groups (p < 0.05). There was no difference between the groups' mean heart rates before the procedure; however, there was a significant difference 10 s after the procedure started and after the procedure (p < 0.05).

Conclusion: Breastfeeding is the most effective method to reduce pain during and after HL procedures in term newborns, followed by SSC and swaddling + holding.

Trial registration: This study was retrospectively registered at ClinicalTrials.gov with the registration number NCT05797532 (date: 04.04.2023).

Background: Acute lymphoblastic leukemia (ALL) is a prevalent hematologic malignancy that primarily affects children. The diagnosis and treatment of pediatric ALL remain challenging. This study aimed to identify differential lipids and metabolites that may hold potential for improving ALL treatment.

Methods: In this retrospective case-control study, serum samples obtained from children with ALL and healthy controls were analyzed. Serum lipidome and metabolome alterations of ALL were analyzed by comparing pediatric patients with ALL with healthy controls based on liquid chromatography high-resolution mass spectrometry analysis of serum lipidomic and metabolomic signatures.

Results: We identified 2,298 lipid features in the serum. Among them, 72 (3.13%) differed significantly in pediatric patients with ALL compared to healthy controls. Notably, sphingolipids (ceramide and sphingomyelin) and phospholipids exhibited the most pronounced changes. Targeted analysis of ceramides revealed significantly elevated levels of Cer 18:0 and Cer 20:0 in the serum of pediatric patients with ALL. Additionally, gut microbial-related lipids (such as sulfonolipids and fatty acid esters of hydroxy fatty acids) showed significant alterations. Metabolomic analysis identified 15 differential metabolites, indicating disrupted nucleotide and amino acid metabolism. Furthermore, the dysregulated lipids and metabolites correlated with various blood indicators, with ceramide and nucleosides positively associated with white blood cell count but negatively correlated with hemoglobin and platelet.

Conclusion: These findings shed light on abnormal molecular signatures contributing to pediatric ALL and may serve as potential biomarker panel for therapy of ALL.

Background: Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in the SLC22A5 gene, with its prevalence and the spectrum of mutations in SLC22A5 varying across races and regions. This study aimed to analyze the clinical and genetic characteristics of PCD patients, including newborns and their mothers, identified by newborn screening (NBS) in Hefei, China.

Methods: The dried blood spot samples from newborns were analyzed using tandem mass spectrometry (MS/MS) from July 2015 to December 2024. Newborns and their mothers with low free carnitine (C0) levels identified during initial screening were subsequently recalled. Next-generation sequencing was employed to analyze gene mutations in patients whose rescreening results indicated that C0 levels remained below the critical reference value.

Results: A total of 897,050 newborns were screened for PCD, and 46 cases were diagnosed, resulting in an incidence rate of 1 in 19,501. Among the screened population, 34 mothers were identified as PCD patients. A total of 26 different variants were detected in the SLC22A5 gene, including four novel variants found in both PCD newborns and their mothers (c.253 C > T, c.976_977delinsAGCAGT, c.384dup, and c.236_271del). Of the 44 PCD newborns tested at our center, seven exhibited homozygous mutations, 35 exhibited compound heterozygous mutations, and two cases showed no detectable gene mutation. The most common mutation was c.1400 C > G (45.88%), followed by c.51 C > G (16.47%) and c.760 C > T (8.24%). Among the 34 PCD mothers, 15 had homozygous mutations and 19 had compound heterozygous mutations; 60.29% of the mutations were c.1400 C > G. The C0 levels in patients with SLC22A5 truncation mutations were significantly lower than those in the non-truncation mutation group (P < 0.05). Furthermore, within the truncation mutation group, the C0 levels of patients with the S467C mutation were higher than those of patients without the S467C mutation (P < 0.05).

Conclusions: MS/MS combined with genetic testing could effectively enhance the diagnostic accuracy of PCD. Our study identified four novel mutations, expanding the variant spectrum of the SLC22A5 gene.