Ital J Pediatr [JOURNAL]
Sun
200 papers
Causal effects of single-carbon metabolism and vitamin levels on autism spectrum disorder risk: a bidirectional Mendelian randomized study.
Zhu J, Yi Y, Ma L … +5 more , Tao S, Sun J, Zhang D, Sun X, Ding K
Ital J Pediatr · 2026 Apr · PMID 41992357 · Full text
BACKGROUND: Observational epidemiology studies suggested a relationship between single-carbon metabolism and vitamin levels with autism spectrum disorder (ASD) risk. We aimed to explore the causal relationship between th...
BACKGROUND: Observational epidemiology studies suggested a relationship between single-carbon metabolism and vitamin levels with autism spectrum disorder (ASD) risk. We aimed to explore the causal relationship between them at the genetic level. METHODS: We performed a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association studies summary statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied other complementary methods, including weighted median, weighted mode, and MR Egger regression. MR Egger and MR pleiotropy residual sum and outlier (MR-PRESSO) are used to detect and correct the effects of horizontal pleiotropy. RESULTS: There were no causal associations between genetically predicted single-carbon metabolism and vitamin levels with ASD risk in IVW analysis (Homocysteine: 95% CI: 0.952–1.082, P = 0.652; Folate in Serum or Plasma: 95% CI: 0.968–1.249, P = 0.143; VB12: 95% CI: 0.989–2.133, P = 0.057; VB6: 95% CI: 0.647–1.247, P = 0.522; VC: 95% CI: 0.794–1.881, P = 0.362; VD: 95% CI: 0.825–1.551, P = 0.443; and VE: 95% CI: 0.87–1.711, P = 0.249). Reversely, we did not find significant causal effects of ASD on single-carbon metabolism and vitamin levels in MR analysis (all P > 0.05). Based on sensitivity analyses, heterogeneity and horizontal pleiotropy are unlikely to distort causal estimates. CONCLUSIONS: The MR study suggests that no evidence of a causal association was found between single-carbon metabolism and vitamin levels with ASD risk. Further studies are needed to validate these conclusions. CLINICAL TRIAL NUMBER: Not applicable.
Associations of systemic inflammatory indices and metabolically healthy vs. unhealthy obesity in children.
Bіlіcі ME
Ital J Pediatr · 2026 Apr · PMID 41987301 · Full text
OBJECTIVE: Childhood obesity, which continues to rise globally, is associated with inflammation-driven metabolic disturbances and increased cardiometabolic risk. Individual variability in metabolic health—independent of...
OBJECTIVE: Childhood obesity, which continues to rise globally, is associated with inflammation-driven metabolic disturbances and increased cardiometabolic risk. Individual variability in metabolic health—independent of obesity severity—has led to the concept of metabolically healthy obesity (MHO). This study aimed to evaluate the relationship between metabolic health status and systemic inflammatory indices in childhood obesity, including analyses adjusted for sex and pubertal stage to account for physiologic developmental changes. METHODS: This retrospective study included children with BMI SDS ≥ 2, categorised as Metabolically Unhealthy Obese (MUO) if they had ≥ 1 of the following: fasting glucose ≥ 100 mg/dL, HOMA-IR ≥ 2.5 (prepubertal) or ≥ 4 (pubertal), triglycerides ≥ 150 mg/dL, HDL ≤ 40 mg/dL, or systolic/diastolic blood pressure ≥ 95th percentile. Children with none of these findings were classified as MHO. Inflammatory indices—neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic immune-response index (SIRI)—were analysed using ROC curves and multivariable regression. Additional analyses adjusted for age, sex, pubertal stage, and BMI SDS were performed to account for developmental influences on inflammatory markers. RESULTS: A total of 388 obese children (58.1% female, mean age 11.5 ± 2.9 years) were included; 35.4% were morbidly obese, and 45.6% were classified as MUO. MUO children had significantly higher white blood cell, neutrophil, and monocyte counts, as well as higher fasting glucose, HOMA-IR, triglycerides, and total cholesterol, with lower HDL levels. Dyslipidemia was the most common metabolic abnormality. SII demonstrated strong discriminatory ability for metabolic health (AUC = 0.854; 82% sensitivity; 72% specificity). SII was positively associated with HOMA-IR, TG/HDL-C, and non-HDL cholesterol (p = 0.006; p = 0.004; p = 0.01, respectively). After adjustment for age, sex, pubertal stage, and BMI SDS, the associations of SII and SIRI with metabolic health status were attenuated but remained directionally consistent, indicating that developmental factors partially influence systemic inflammatory responses. CONCLUSION: The high prevalence of MUO among obese children highlights their substantial cardiometabolic risk burden. SII and SIRI appear to be promising, readily accessible biomarkers for identifying metabolic deterioration, showing meaningful correlations with key cardiometabolic risk indicators. These indices may support clinicians in early detection and monitoring of metabolic dysfunction in pediatric obesity, even when accounting for developmental stage.
A nomogram for early prediction of pertussis-associated pneumonia in children: a retrospective clinical study.
Ren J, Chen D, Zhang T … +2 more , Ren Y, Sun X
Ital J Pediatr · 2026 Apr · PMID 41987214 · Full text
BACKGROUND: Pertussis, an acute respiratory infection caused by Bordetella pertussis, has recently shown a global resurgence. Pneumonia represents one of its most frequent and severe complications. The present study aime...
BACKGROUND: Pertussis, an acute respiratory infection caused by Bordetella pertussis, has recently shown a global resurgence. Pneumonia represents one of its most frequent and severe complications. The present study aimed to identify risk factors for pertussis-associated pneumonia and to develop a predictive model for early identification of high-risk pediatric patients. METHODS: A retrospective analysis was performed on 123 children hospitalized with pertussis at the Children's Hospital Affiliated to Zhengzhou University between 1 June 2024 and 31 December 2024(training cohort). Using univariate analysis, least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis, identified the predictors for pertussis-associated pneumonia. An independent cohort enrolled between 1 January 2025 and 31 July 2025, was used for external validation cohort. Receiving operating characteristic curve (ROC), calibration plots, decision curve analysis (DCA), and clinical impact curves (CIC) were used to evaluate the performance of the model. RESULTS: We identified five independent predictors of pertussis-associated pneumonia: white blood cell count (WBC; OR = 1.112, 95% CI: 1.012-1.221), interleukin-6 (IL-6; OR = 1.153, 95% CI: 1.049-1.267), lymphocyte percentage (Lym%; OR = 1.045, 95% CI: 1.013-1.078), interleukin-17a (IL-17a; OR = 1.209, 95% CI: 1.024-1.427), and Co-infection (OR = 3.096, 95% CI: 1.260-7.610). The area under the receiver operating characteristic curve (AUC) was 0.824 (95% CI: 0.747-0.900) in the training cohort and 0.792 (95% CI: 0.718-0.865) in the external validation cohort. The Hosmer-Lemeshow test indicated good calibration (P = 0.590 in the training cohort; P = 0.735 in the external validation cohort). Decision curve analysis and clinical impact curves confirmed clinical utility. CONCLUSION: A clinically useful nomogram model was developed for early prediction of pertussis-associated pneumonia in children. Application of this model may assist clinicians in promptly identifying high-risk patients and implementing timely interventions to improve outcomes.Notably, this study had a small sample size (n = 123) relative to the five predictors, and the external validation cohort was from the same center, which may limit the model's generalizability to heterogeneous clinical settings.
Persistent use of broad-spectrum antibiotics for suspected community acquired urinary tract infections in children in Italian primary care settings.
Gres E, Veronese P, Brigadoi G … +4 more , Vego Scocco M, Nicolini G, Dona' D, Barbieri E
Ital J Pediatr · 2026 Apr · PMID 41965827 · Full text
BACKGROUND: Urinary tract infections (UTIs) are common in children, and diagnosis is often difficult due to nonspecific symptoms, urine collection challenges, and increasing antimicrobial resistance. The emergence of ESB...
BACKGROUND: Urinary tract infections (UTIs) are common in children, and diagnosis is often difficult due to nonspecific symptoms, urine collection challenges, and increasing antimicrobial resistance. The emergence of ESBL-producing organisms highlights the need for locally informed guidelines supported by antibiotic stewardship activities. This study aimed to describe antibiotic prescribing patterns for suspected community-acquired UTIs (CA-UTIs) in the Italian primary care setting among children aged 0–14 years and to assess the impact of the 2019 Italian Society of Paediatric Nephrology (SINePe) guidelines update on prescribing behaviour in children aged 2 months to 3 years. METHODS: We conducted a database analysis including Italian children aged 0–14 years between 2015 and 2024 using data from the Pedianet database, which contains anonymized electronic health records of over 275,000 children. CA-UTI episodes were identified through ICD-9-CM codes and free-text searches, then manually validated. All antibiotic prescriptions (classified by ATC codes and AWaRe classification) issued during each episode and associated to the CA-UTI were included. An interrupted time-series (ITS) analysis using a Poisson model was conducted to evaluate the impact of the 2019 national consensus guidelines on yearly antibiotic prescribing patterns in children aged 2 months to 3 years with a first episode of CA-UTI. RESULTS: From 2015 to 2024, 32,519 suspected CA-UTI episodes in 26,650 children were included. The majority of children experienced a single episode (79.9%). Co-amoxiclav was the most frequently prescribed antibiotic, followed by third-generation cephalosporins, which remained common across the study period. Fosfomycin use increased with age and was more frequent among older children. Over 2550 first CA-UTI episodes were included in the ITS analysis showing no significant changes in prescribing patterns following the 2019 guideline update. Similar trends were confirmed when restricting the analysis to empiric antibiotic treatments. CONCLUSION: Co-amoxiclav remains the first-line empiric therapy for paediatric CA-UTIs in Italian primary care, although third-generation cephalosporins are still frequently prescribed despite revised recommendations. These findings highlight the need for continued antimicrobial stewardship efforts and monitoring to optimize paediatric UTI management in the community setting.
Role of IL-6 gene polymorphisms in children with autism spectrum disorders.
Abdullah NM, Moness HM, Ali MWE … +3 more , Abdelsamei EM, Hassan EE, Meshref DA
Ital J Pediatr · 2026 Apr · PMID 41965825 · Full text
BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by impairment in social interaction, and communication skills, along with restricted or repetitive behaviors. The diagnosis...
BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by impairment in social interaction, and communication skills, along with restricted or repetitive behaviors. The diagnosis of ASD depends on behavioral parameters. Numerous studies have reported immune system abnormalities and proposed a potential role of autoimmunity in the pathogenesis of ASD. This study aims to assess the correlation between specific cytokines, such as interleukin-6 (IL-6), and particular IL-6 polymorphisms, including IL-6-174G/C (rs1800795) gene polymorphism, IL-6-572 C/G (rs1800796) gene polymorphism and IL-6-597G/A (rs1800797) gene polymorphism among children with ASD. METHODS: The current study included 100 children with ASD were recruited during their regular follow up to Pediatric Neuro-Psychiatry Clinic of Minia University Hospital of Children. They diagnosed according to DSM-5 ASD criteria. A another 100 children were recruited as control group by simple randomly selected school (pre & elementary school) in Mina Governate, Upper Egypt, their ages and sex matched with the ASD children, they were apparently neuropsychiatric and developmentally normal and free from any chronic systemic illness. The participants were assessed for serum IL-6 levels and single-nucleotide changes in IL-6-174G/C, IL-6-572 C/G and IL-6-597G/A gene polymorphisms. RESULTS: The prevalence of the GG genotype and G allele of the IL-6-174G/C gene polymorphism was significantly higher in ASD patients compared to healthy control (P value = 0.0002, 0.03 respectively). In contrast, the GC genotype and C allele of IL-6 -174G/C gene polymorphism were significantly elevated in the control group compared to children with ASD, indicating a protective role against ASD in the Egyptian population. The prevalence of the CG genotype, GG genotype, and G allele of the IL-6-572 C/G gene polymorphism was significantly higher in ASD patients compared to control individuals, indicating an increased risk of ASD within the Egyptian population. The IL-6-597G/A gene polymorphism analysis revealed no significant differences between the two groups in GG and GA genotypes or allelic frequencies. Nevertheless, the AA genotype was only found in the autistic group. Furthermore, ASD patients exhibited significantly higher serum levels of IL-6 than the healthy controls. The GG genotype distribution of IL-6-174G/C gene polymorphism was significantly associated with increased serum levels of IL-6. CONCLUSION: The IL-6 (-174G/C) gene polymorphism (GG genotype) was associated with ASD. Moreover, the (CG + GG) genotypes of IL-6-572 C/G gene polymorphism were associated with ASD, and the (AA genotype) of IL-6-597G/A gene polymorphism was detected only in ASD. This indicates their role in the increased incidence of ASD among the Egyptian population. In addition, IL-6 serum level was significantly elevated in ASD.
Guidelines on diagnosis and management of gastroesophageal reflux disease in infants, children and adolescents: a joint consensus from Italian pediatric societies (SIP and SIGENP) -part I. diagnosis.
Salvatore S, Strisciuglio C, Bozzola E … +14 more , Cappa S, Corsello A, Nardo GD, Fuoti M, Gulino A, Mameli C, Orso M, Pensabene L, Polistena B, Tambucci R, Vassallo F, Romano C, Staiano A, Italian Society of Pediatrics (SIP) and of The Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP)
Ital J Pediatr · 2026 Apr · PMID 41965728 · Full text
BACKGROUND: Gastroesophageal reflux disease (GERD) is a common reason for referral to pediatric and gastroenterology clinics. Still, uncertainty and variability exist in the evaluation, diagnostic approaches and manageme...
BACKGROUND: Gastroesophageal reflux disease (GERD) is a common reason for referral to pediatric and gastroenterology clinics. Still, uncertainty and variability exist in the evaluation, diagnostic approaches and management among different age groups and clinicians. This study aimed to report the results of a Guidelines process and an Italian expert Consensus focusing on the diagnosis of GERD in children to improve the clinical approach to these patients. METHODS: A multidisciplinary board of 16 participants identified eight PICO (Population/Patient/Problem, Intervention, Comparator and Outcome) questions, including definition, signs and symptoms, risk factors, diagnostic tests, treatment and prognosis of gastroesophageal reflux (GER) and GERD in children: four PICO questions were related to the diagnosis of GERD. Four databases (PubMed/Medline, Embase, Web of Science and Google Scholar) were searched from their inception to May 11, 2024, limited to children (0–18 years) and English language. For each PICO question a specific search string was developed. Guidelines, systematic reviews and clinical studies on diagnosis and management in children were considered to formulate evidence-based recommendations. Agreement was defined based on a 9-point Likert scale. A two-round Delphi method was conducted and consensus was defined as ≥ 80% agreement or disagreement. This paper focused on clinical symptoms and diagnosis of GER and GERD in pediatric ages. RESULTS: 123 studies were included that satisfied systematic research criteria. The panel provided 14 recommendations on diagnosis of GER and GERD and practice points for specific questions to clarify some clinical issues. CONCLUSION: Symptoms of GER(D) are common in the pediatric population while regurgitation is frequently reported in the first months of life. In infancy symptoms mostly disappear spontaneously or after dietary modification. In infants and children with esophageal or extresophageal persistent symptoms, esophageal pH-MII monitoring and endoscopy are indicated to detect and characterize reflux episodes, phenotypes of GERD and esophagitis. In older children and adolescents reporting typical heartburn or in those with severe neurological impairment, a time-limited empirical trial of PPI can be considered as an initial diagnostic approach, with further testing reserved for non-responders.
Guidelines on diagnosis and management of gastroesophageal reflux disease in infants, children and adolescents: a joint consensus from Italian pediatric societies (SIP and SIGENP) -Part II: management.
Salvatore S, Strisciuglio C, Bozzola E … +15 more , Cappa S, Corsello A, Di Nardo G, Fuoti M, Guadagni L, Gulino A, Mameli C, Orso M, Pensabene L, Tambucci R, Vassallo F, Romano C, Staiano A, Italian Society of Pediatrics (SIP), of The Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP)
Ital J Pediatr · 2026 Apr · PMID 41964096 · Full text
BACKGROUND: Suspected gastroesophageal reflux disease (GERD) is one of the most common reasons for referral to pediatric and gastroenterology clinics, and proton pump inhibitors (PPIs) are frequently prescribed. Currentl...
BACKGROUND: Suspected gastroesophageal reflux disease (GERD) is one of the most common reasons for referral to pediatric and gastroenterology clinics, and proton pump inhibitors (PPIs) are frequently prescribed. Currently, there is still wide heterogeneity in treatment, especially in neonates and extraesophageal presentations. This article aimed to provide guidelines and a consensus of Italian experts on the management of GERD in infants, children, and adolescents, in order to improve the care and treatment of these patients. METHODS: A multidisciplinary pediatric panel identified four key clinical questions (PICOs) regarding pharmacological and non-pharmacological treatments, surgical intervention, and prognosis of pediatric GERD. Four databases (PubMed/Medline, Embase, Web of Science, and Google Scholar) were searched from inception to May 2024, using a specific search string for each PICO and limiting the search to children (0–18 years) and to English language. Previous pediatric guidelines, systematic reviews, and clinical trials focused on the treatment of GERD were considered to formulate evidence-based recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and AGREE II systems were used to assess study quality; a 9-point Likert scale was used to rate the recommendations. A two-round Delphi method was conducted to reach consensus, defined as ≥ 80% agreement or disagreement. RESULTS: The systematic review identified three previous pediatric guidelines, eight systematic reviews, 83 RCTs, and three observational studies. The panel provided 26 recommendations regarding the management and treatment of GERD in pediatric patients. All reached consensus, with the majority expressing strong support for the intervention. The panel also provided practice insights for each PICO to improve the clinical application and clarity of these guidelines. CONCLUSION: Regurgitation is common in infants, but in most cases, no treatment is necessary. When regurgitation causes discomfort, a brief trial of alginate or thickened formulas or a cow’s milk elimination diet may be considered, particularly if other symptoms, including crying and dermatitis, are associated. For children who complain of heartburn or have severe neurologic deficits, a short course of empirical PPIs treatment may be considered, monitoring the clinical response and testing if no improvement is seen. PPIs are recommended in infants and children with reflux esophagitis, or acid reflux detected by esophageal pH monitoring. Children at high- risk for chronic GERD requiring prolonged treatment and multidisciplinary care have been identified. Surgery should be considered for severe or complicated GERD after a comprehensive diagnostic workup and optimal pharmacological management.
Implementation of an antimicrobial stewardship program in Alexandria University Children's Hospital: an interventional study.
Refaei SES, El-Attar L, Amine AEK … +2 more , Meheissen MA, Hassan EH
Ital J Pediatr · 2026 Apr · PMID 41964087 · Full text
BACKGROUND: Antimicrobial resistance (AMR) represents a threat to global public health. The antibiotics' effectiveness against a variety of infections consequently has been declined with increasing morbidity, mortality,...
BACKGROUND: Antimicrobial resistance (AMR) represents a threat to global public health. The antibiotics' effectiveness against a variety of infections consequently has been declined with increasing morbidity, mortality, and treatment failure. To combat this, the implementation of Antimicrobial Stewardship Programs (ASPs) is essential for slowing the spread of resistant pathogens. AIM OF THE WORK: The current study aimed to assess the outcomes following implementation of Antimicrobial Stewardship Program (ASP) at Alexandria University Children's Hospital. METHOD: The study was conducted over nine months in a general pediatric ward. First, the medical records and microbiological reports were reviewed to establish tailored antibiotic guidelines. During the intervention phase, the ASP focused on prospective audits and physicians' education. The program's impact was evaluated through several key metrics: adherence to the guidelines, patient outcome (mortality rate and length of stay) and antibiotic consumption (expenditure, days of therapy, and treatment duration). All statistical analyses were conducted using IBM SPSS version 20.0. RESULTS: 219 patients in the preintervention phase were compared to 214 patients (post-intervention). Following ASP, the use of single antibiotics increased in post-intervention (69.6% versus 26%). During the study period, 70 interventions were required with a high acceptance rate (59%). The mean length of hospital stays decreased [10.80 (3-26) versus 12.89 (4-33) days], and both DOT/1000 patients and the average cost of antibiotics decreased (27.82% and 44.94%, respectively). Following ASP, the use of Tigecycline (-100%), Meropenem (-57.79%), and Vancomycin (-46.35%) reduced with an increase in the use of Cefotaxime (80.43%), Ceftriaxone (20.27%), and Ceftazidime (62.87%). CONCLUSION: The implementation of institutional guidelines along with Prospective Audit and Feedback (PAF) was associated with improvements in antibiotic utilization, particularly in the resource-limited settings. CLINICAL TRIAL NUMBER: Not applicable.
Active treatment vs. expectant management of patent ductus arteriosus in preterm infants: critical analysis of a meta-analysis.
Dani C, Agosti M, de Luca D
Ital J Pediatr · 2026 Apr · PMID 41964028 · Full text
A recent meta-analysis on the active versus expectant management of patent ductus arteriosus in preterm infants, including 10 randomized control trials involving 2035 infants, found that the incidence of death at 36 week...
A recent meta-analysis on the active versus expectant management of patent ductus arteriosus in preterm infants, including 10 randomized control trials involving 2035 infants, found that the incidence of death at 36 weeks or moderate to severe bronchopulmonary dysplasia (BPD) and of death was higher in the active treatment group. The accompanying editorial suggested that “the use of early routine pharmacologic treatment no longer appears to be justifiable”. However, this meta-analysis is based on highly heterogeneous studies due to different diagnostic criteria used to define hemodynamically significant PDA, postnatal age at which the echocardiography was performed, pharmacological treatment, high frequency of open label treatment in the placebo/expectant management group. Moreover, authors did not explain the reduction in mortality that they reported. We concluded that clinical and methodological heterogeneity among studies may not be detected by statistical heterogeneity tests, reducing the interpretability of the results and weakening causal inferences. The high occurrence of open-label treatment indicates the need to perform a per-protocol analysis, which would have been possible if the authors had performed an individual participant data network meta-analysis. Furthermore, the current lack of pathophysiological plausibility suggests caution in interpreting the results of this meta-analysis.
Basilar artery flow velocities and optic nerve sheath diameter as adjuvant tools for early diagnosis of hypoxic ischemic encephalopathy in neonates.
Farag MM, Thabet MAEH, Ahmed IS … +1 more , Halawa HMA
Ital J Pediatr · 2026 Apr · PMID 41963972 · Full text
OBJECTIVE: We investigated potentiality ultrasonography measured optic nerve sheath diameter (ONSD) and basilar artery (BA) velocities to identify neonates with HIE-requiring-TH. METHODS: Study was of a case-control-desi...
OBJECTIVE: We investigated potentiality ultrasonography measured optic nerve sheath diameter (ONSD) and basilar artery (BA) velocities to identify neonates with HIE-requiring-TH. METHODS: Study was of a case-control-design. Thirty- five neonates with mild-to-severe HIE admitted to NICU of Alexandria-University-Maternity-Hospital and were monitored by ultrasound-measured ONSD and BA velocities, in first-12-hours, during TH, and after rewarming. First scan measures of patients were compared to healthy-control-neonates. Comparative statistics, ROC-curves, and correlation of different clinical and imaging parameters were used in analysis. RESULTS: Mean value of left-and-right-ONSD measurements in control group (0.31 cm, 0.30 cm, respectively) were significantly higher than asphyxiated-group (0.35 cm), with p-value<0.001. ONSDs of > 0.32 cm in right-and-left eyes carry 91% and 88% sensitivity, respectively, and 100% specificity in identifying patients with mild-to-severe HIE. Resistive index (RI) of BA decreased and EDV of BA increased in HIE-patients than healthy-control-neonates, with p value<0.001. Left-and-right-ONSD diameters are negatively correlated with BA-RI, with r=-.432; p < .01and r=-.34; P.046, respectively. ONSDs in both eyes, BA-RI and BA-EDV showed significant changes throughout three time points in HIE-patients. CONCLUSION: ONSD and BA-velocities can help in early identification of asphyxiated-neonates and therefore can be used to select patients candidate for TH. They also help in monitoring of asphyxiated-patient before, during and after TH.
Making regional comparisons policy-ready: clarified, standardised methods and region-wide RSV hospital discharge estimates from Emilia-Romagna, Italy.
Montalti M, Frasca G, Mario SD … +4 more , Perrone E, Giroldini R, Cintori C, Diegoli G
Ital J Pediatr · 2026 Apr · PMID 41963953 · Full text
Respiratory syncytial virus (RSV) prophylaxis with nirsevimab was introduced in Italy from the 2024–2025 epidemic season. The preprint “Impact of Regional heterogeneity of RSV infection prophylaxis on bronchiolitis in It...
Respiratory syncytial virus (RSV) prophylaxis with nirsevimab was introduced in Italy from the 2024–2025 epidemic season. The preprint “Impact of Regional heterogeneity of RSV infection prophylaxis on bronchiolitis in Italy” provides timely information for clinicians and health-system planners; however, several methodological specifications require clarification to ensure reproducibility and valid cross-regional comparability, particularly for the Emilia-Romagna Region. In Emilia-Romagna, programme choices were supported by a retrospective analysis of routinely collected hospital discharge and birth registry data (2015–2023), documenting that most of the RSV-associated hospital-admission burden is concentrated in infancy and follows a marked seasonal pattern, with severe outcomes largely confined to the first year of life. This evidence informed a risk-stratified approach during the initial roll-out. Using region-wide hospital discharge records from all Emilia-Romagna hospitals, we observed larger reductions between October 2023–March 2024 and October 2024–March 2025 than those presented as “regional” estimates in the preprint: total hospitalisations decreased from 1384 to 607 (−56.1%) among children aged < 14 years and from 1131 to 364 (−67.8%) among infants aged < 1 year; paediatric intensive care unit admissions decreased from 136 to 32 (−76.5%) and from 126 to 23 (−81.7%), respectively. To maximise the policy value of cross-regional comparisons and to support a more uniform, evidence-based national strategy in future seasons, key methods should be reported in a clear and standardised way.
Macrolide-induced hypersensitivity reactions in the pediatric population.
Caimmi S, Liotti L, Riscassi S … +11 more , Rosset G, Bottau P, Bianchi A, Crisafulli G, Franceschini F, Mori F, Saretta F, Valluzzi RL, Buono EV, Marseglia GL, Caffarelli C
Ital J Pediatr · 2026 Apr · PMID 41933421 · Full text
Macrolides are widely prescribed antibiotics in pediatric practice and are commonly used as alternatives in children with suspected or confirmed beta-lactam allergy. Although generally considered safe and associated with...
Macrolides are widely prescribed antibiotics in pediatric practice and are commonly used as alternatives in children with suspected or confirmed beta-lactam allergy. Although generally considered safe and associated with low allergenic potential, hypersensitivity reactions to macrolides do occur and may lead to inappropriate drug avoidance. This review critically appraises the current evidence on macrolide-induced hypersensitivity reactions in the pediatric population, focusing on clinical manifestations, diagnostic approaches, cross-reactivity, and management strategies. Hypersensitivity reactions to macrolides are estimated to occur in 0.4–3% of treatments, with immediate reactions such as urticaria and angioedema being the most frequently reported. Anaphylaxis is exceedingly rare, while delayed reactions, particularly maculopapular exanthema, represent the most common non-immediate presentations. Severe cutaneous adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, and fixed drug eruptions, have been reported but remain exceptional in children. The diagnostic workup of suspected macrolide allergy is challenging due to the limited sensitivity and poor predictive value of skin tests and the lack of validated in vitro assays. Current evidence supports the use of drug provocation tests as the gold standard for diagnosis, particularly in children with non-severe, skin-limited reactions. Recent guidelines increasingly favor direct oral challenge without prior skin testing in low-risk pediatric patients. Studies consistently demonstrate that most children with suspected macrolide allergy tolerate re-exposure, confirming that true allergy is uncommon. Cross-reactivity among macrolides appears to be infrequent in children but may occur, especially in severe reactions. Desensitization protocols, although not standardized, have been successfully applied in selected pediatric cases when macrolides are indispensable. Overall, accurate diagnosis through appropriate testing is essential to avoid unnecessary antibiotic restrictions, ensure optimal antimicrobial therapy, and reduce the burden of incorrect allergy labeling in pediatric patients.
Seizures and Apneas as clinical manifestations of brain lesions in term infants: a single center experience.
Skubisz A, Calandrino A, Vinci F … +17 more , Massirio P, Andreato C, Caruggi S, Battaglini M, Parodi A, Brigati G, Malova M, Bertamino M, Tortora D, Severino M, Resaz M, Amadori E, Uccella S, Nobili L, Rossi A, Striano P, Ramenghi LA
Ital J Pediatr · 2026 Apr · PMID 41933360 · Full text
BACKGROUND: Seizures and apneas are always concerning symptoms in near-term and term newborns, but finding a clear explanation is not always easy. In addition, it is not always clear which investigations should be prompt...
BACKGROUND: Seizures and apneas are always concerning symptoms in near-term and term newborns, but finding a clear explanation is not always easy. In addition, it is not always clear which investigations should be promptly conducted. We aimed to evaluate the relationship (or lack thereof) between apneas and seizures and the role of MRI and EEG in their investigation. METHODS: We conducted a retrospective analysis including infants born at ≥ 36 + 0 weeks of gestational age who presented with seizures or apneas soon after birth and underwent brain magnetic resonance imaging (MRI) during their stay at a tertiary-level academic Neonatal Intensive Care Unit (NICU) in Italy between January 2016 and July 2024. Brain MRI was systematically planned for to all term infants with clinical presentations of seizures, recurrent unexplained apneas, or abnormal aEEG/EEG. RESULTS: Our inclusion criteria were met by 58 (18%) patients; 31/58, (53%) presented with seizures and 27/58 (47%) with apneas without overt seizures manifestation. Apgar scores at 1 and 5 min were similar across clinical subgroups. Neurophysiological monitoring (EEG/aEEG) was performed in 50/58 (86%) infants; all 31 infants with clinical motoric seizures had abnormality on the EEG, though in 20 (65%) apneas were still their primary manifestation. Of the 27 presenting with apneas without documented EEG seizures, 6 experienced apneas only shortly after birth, 6 only with feeding (EEGs not done consistently) and of the other 15 the EEG was normal in the 12 who were monitored. Abnormal MRI findings were present in 27/31 (87%) infants with seizures and in 10/27 (37%) in the apnea only group. Focal arterial territory ischemic stroke was the commonest single diagnosis. Seizure-related apneas were associated with punctate white matter injury, focal ischemic stroke and severe intraventricular hemorrhage. CONCLUSIONS: Seizures and apneas occur with similar frequency in newborns born near or at term investigated with cerebral MRI for seizures and apneeas-related encephalopathy. The majority of infants had abnormal brain imaging, almost all of an ischaemic or haemorrhage nature. We strongly recommend brain imaging to assess potential brain injury in (near)term neonates with either of these clinical signs.
Comparison of two targeted rescue treatments after the first week of expectant managment for very preterm infants with hemodynamically significant patent ductus arteriosus: a prospective study.
Wang L, Xu S, Shi H … +6 more , Zhang C, Wang B, Sun Z, Li M, Gao T, Gao X
Ital J Pediatr · 2026 Apr · PMID 41928306 · Full text
BACKGROUND : To investigate the clinical value of early expectant management of very preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA), and the efficacy and safety of rescue treatment with...
BACKGROUND : To investigate the clinical value of early expectant management of very preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA), and the efficacy and safety of rescue treatment with oral acetaminophen or high-dose ibuprofen. METHODS: The very preterm infants with hsPDA (gestational age ≤ 32 weeks and age 4-6 days) who were admitted to the neonatal intensive care unit of Xuzhou Central Hospital between February 2022 and December 2024 were enrolled in the study. If the patient still met the diagnostic criteria of hsPDA after 3-4 days of expectant management, the rescue treatment shall be given. They were randomly divided into the acetaminophen group (oral acetaminophen 15 mg/kg, once every 6 hours for 3 days) and the high-dose ibuprofen group (oral ibuprofen 20 mg/kg for the first time, 10 mg/kg for the 24 hours and the 48 hours respectively). Before and after treatment, routine blood tests, biochemical items (including serum Cystatin C, serum creatinine, alanine aminotransferase and total serum bilirubin), urinary Cystatin C, B-type natriuretic peptide, and fecal occult blood were measured; bedside echocardiography and brain standard ultrasound were performed; and urine output and complications were recorded. The data were analyzed by t-test, rank sum test and chi-square test with SPSS 20.0 statistical software. RESULTS: 167 (54.4%) of 307 very preterm infants with hsPDA showed spontaneous closure in the first 7-10 days of life. There was no significant difference in the success rate of rescue treatment between the acetaminophen group and the high-dose ibuprofen group [82.0% (50/61) vs. 77.8% (49/63), P=0.561]. During rescue treatment, the upper gastrointestinal bleeding rate, positive fecal occult blood tests and oliguria rate of high-dose ibuprofen group were higher than those of the acetaminophen group, but the difference was not statistically significant (P>0.05). The incidence of stage Ⅱ-Ⅲ necrotizing enterocolitis and stage Ⅲ-Ⅳ intraventricular hemorrhage in the two groups were lower, and the difference was not statistically significant (P>0.05). After rescue treatment, the serum Cystatin C of high-dose ibuprofen group was higher than that of acetaminophen group [(1.66±0.30) mg/L vs. (1.55±0.24) mg/L], the urinary Cystatin C of high-dose ibuprofen group was higher than that of acetaminophen group [(80.00±32.96) ng/mL vs. (66.50±26.77) ng/mL], and the 24-hours urine output was lower than that of acetaminophen group [(2.66±1.32) ml/(kg•h) vs. (3.29±1.15) ml/(kg•h)], with statistical significance (P=0.018, 0.014, 0.290). After rescue treatment, there were no significant differences in serum creatinine, platelet count, B-type natriuretic peptide, alanine aminotransferase, and total serum bilirubin between the two groups (P>0.05). CONCLUSION: In the early stage (7-10 days after birth) of very preterm infants with hsPDA, the spontaneous closure rate of hsPDA during expectant management can reach more than 50%. After the failure of expectant management, rescue treatment with oral acetaminophen or high-dose ibuprofen can be started on the 7th to 10th day after birth, and the success rate is about 80%, and was relatively safe. The effect of oral high-dose ibuprofen on renal function may be greater than that of acetaminophen. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCRT2200056444. Registered 06 February 2022, https://www.chictr.org.cn/showproj.html?proj=151092.
Perinatal factors and their association with cardiometabolic profile in schoolchildren.
Mansour KMK, Tornquist L, Mortensen N … +3 more , Pfeiffer KA, Paiva DN, Reuter CP
Ital J Pediatr · 2026 Mar · PMID 41918105 · Full text
BACKGROUND: Developmental origins of health and disease suggest a link between the periconceptual, fetal, and early infant phases of life and the persistent development of metabolic disorders. Therefore, this study aimed...
BACKGROUND: Developmental origins of health and disease suggest a link between the periconceptual, fetal, and early infant phases of life and the persistent development of metabolic disorders. Therefore, this study aimed to verify the associations between perinatal variables and cardiometabolic profiles in school-aged children and adolescents. METHODS: Retrospective study that used cross-sectional data from a database of a larger study named "Schoolchildren's health". The study was carried out using a sample comprising children and adolescents, ranging from 6 to 17 years old from both genders. All participants were enrolled in private and public schools in the city of Santa Cruz do Sul, Brazil. A self-administered questionnaire was applied to children and parents, then anthropometric measurements of body mass index (BMI), body fat percentage (BF%), and waist circumference (WC) were obtained, followed by a cardiorespiratory fitness (CRF) test. The association of perinatal variables with BMI, WC, BF%, and CRF was tested by multiple linear regression, using the "Enter" input method, being the unstandardized coefficient (B) and 95% confidence intervals of the associations were estimated. Data were analyzed with Statistical Package for the Social Sciences software, version 23.0 (IBM, Armonk, NY, USA). Statistical significance was established as p < 0.05. RESULTS: A total of 1,431 children and adolescents were evaluated, with 803 (56.1%) of them being females and white subjects (83%) with mean age of 11.48 ± 2.75 years. Associations between perinatal factors and anthropometric measurements were found birth weight (BW) and BMI (B:1.13; 95%CI:0.74;1.51), BW and WC (B:2.20; 95%CI:1.37;3.04), BW and BF% (B:1.84; 95%CI:0.83;2.84). Gestational age also had associations with BMI (B:1.00; 95%CI:0.25;1.74); WC (B:1.88; 95%CI:0.25;3.50) and CRF (B:-168.91; 95%CI:-299.53;-38.29). Complications during pregnancy and BMI (B:0.48; 95%CI:0.02;0.93) and cesarean birth and BMI (B:0.43; 95%CI:0.01;0.86). CONCLUSIONS: Associations exist between perinatal factors and future cardiometabolic profiles. It is imperative to establish and reinforce efforts geared towards enhancing the health literacy of both adolescent boys and girls, along with pregnant women.
A clinical-biomarker fusion model for risk prediction of coronary artery lesions in Kawasaki disease.
Zhao Q, Miao Y
Ital J Pediatr · 2026 Mar · PMID 41918102 · Full text
OBJECTIVE: This study aimed to develop and validate a predictive model integrating multidimensional clinical indicators and laboratory biomarkers for the early and precise assessment of coronary artery lesion (CAL) risk...
OBJECTIVE: This study aimed to develop and validate a predictive model integrating multidimensional clinical indicators and laboratory biomarkers for the early and precise assessment of coronary artery lesion (CAL) risk in Kawasaki disease. METHODS: A retrospective analysis was conducted on 320 children with Kawasaki disease admitted between January 2020 and June 2024. The sample size was calculated using PASS 2021 software (α = 0.05, 1-β = 80%), with post-hoc power exceeding 85%. Patients were randomly allocated into a training set (n = 224) and a validation set (n = 96) in a 7:3 ratio. In the training set, univariate analysis identified CAL-associated indicators (P < 0.05). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for variable compression and feature selection. The core variables were incorporated into a multivariate logistic regression to identify independent risk factors. Based on these factors, three machine learning models—Gradient Boosting Machine (GBM), Support Vector Machine (SVM), and Convolutional Neural Network (CNN)—were constructed. Model performance was evaluated using the AUC, calibration curves, and DCA. Interpretability was analyzed using SHapley Additive exPlanations (SHAP) values. RESULTS: No significant differences in baseline characteristics were observed between the training and validation sets (P > 0.05). Univariate analysis identified seven significant indicators. LASSO regression refined these to five core variables. Multivariate logistic regression confirmed all five as independent risk factors for CAL (P < 0.05). Among the machine learning models, the GBM model demonstrated superior performance, with AUC of 0.872 (95% CI: 0.798–0.945) in the training set and 0.790 (95% CI: 0.623–0.957) in the validation set. Calibration curves were closest to the ideal line. DCA indicated net clinical benefit across a wide threshold probability range. SHAP analysis provided intuitive prediction interpretability. CONCLUSION: An integrated clinical-biomarker model was developed and validated for the early prediction of CAL in Kawasaki disease. The model demonstrates good discriminative ability, calibration, and clinical utility. and provides a promising tool for the early identification of high-risk children and the optimization of intervention strategies. CLINICAL TRIAL NUMBER: Not applicable.
Trends in otitis media burden among BRICS from 1990 to 2023 and projections to 2040: an age-period-cohort analysis based on the 2023 global burden of disease study.
Chen X, Yang X, Gu D
Ital J Pediatr · 2026 Mar · PMID 41896970 · Full text
BACKGROUND: Otitis media (OM) is a prevalent ear disease that can lead to severe complications, including hearing loss. As significant emerging economies, the BRICS countries warrant focused attention on the evolving tre...
BACKGROUND: Otitis media (OM) is a prevalent ear disease that can lead to severe complications, including hearing loss. As significant emerging economies, the BRICS countries warrant focused attention on the evolving trends in OM burden. OBJECTIVE: To systematically analyze trends in OM burden in BRICS from 1990 to 2023 and forecast developments. METHODS: Using data from the 2023 GBD study, we analyzed the age-standardized incidence rate (ASIR) and age-standardized disability-adjusted life year (DALY) rate (ASDR) of OM in BRICS countries from 1990 to 2023, along with their temporal trends. The age-period-cohort model was employed to dissect age, period, and cohort effects on disease burden. Trends between 2024 and 2040 were projected using a Bayesian age-period-cohort model. RESULTS: Over the 33 years, the ASIR of OM remained relatively stable across countries, while the ASDR showed a significant decline, with China exhibiting the largest reduction (31.348%). Females consistently showed higher ASIR but lower ASDR than males across all five countries. Within BRICS, the OM burden was predominantly concentrated among children aged 0-9 years. Period effect analysis revealed an overall decreasing trend in DALY rates. Incidence rates remained stable or showed a slight decrease in most countries, with minor increases observed in India and Brazil. Birth cohort analysis revealed a sharp decline in disease burden among recent birth cohorts in China, but a gradual increase among those born since the 1950s in India. Net drift analysis demonstrated a consistent decline in DALY rates across all countries, with China showing the greatest annual decrease (-1.549%/year). In contrast, India (0.007%/year) and Brazil (0.003%/year) exhibited slight increases in incidence rates. Projections for 2024-2040 indicate a continued downward trend in ASIR for Brazil, China, and India, while Russian Federation and South Africa are projected to experience sustained increases. ASDR is projected to rise in all countries except India. CONCLUSION: Over 1990-2023, ASIR of OM in BRICS remained stable, while ASDR declined. Countries should improve the quality of care to effectively reduce the disease burden of OM, based on their own epidemiological trends.
Seasonal allergic rhinitis in children: diagnostic markers of extreme allergic phenotype formation.
Kryuchko TO, Shcherbak VV, Tkachenko OY … +3 more , Nesina IM, Poda OA, Melnyk MO
Ital J Pediatr · 2026 Mar · PMID 41896900 · Full text
BACKGROUND: Patients with severe allergic rhinitis may encounter an elevated risk of developing asthma and other associated allergic conditions. It is known that "allergic rhinitis" and "allergic rhinitis + asthma" are t...
BACKGROUND: Patients with severe allergic rhinitis may encounter an elevated risk of developing asthma and other associated allergic conditions. It is known that "allergic rhinitis" and "allergic rhinitis + asthma" are two clinically distinct phenotypes of allergic rhinitis. Consequently, the aim of our study was to establish the diagnostic criteria for the progression of the allergic phenotype in children with seasonal allergic rhinitis (SAR). METHODS: This cohort study included 47 patients aged between 6 to 17 years diagnosed with SAR, who were categorised into two groups: SAR/SAR with associated allergic conjunctivitis (AC) (Group 1), SAR with concomitant asthma/atopic dermatitis (Group 2). All participants underwent assessments to evaluate their Quality of Life (QoL), as well as the overall severity of nasal and non-nasal symptoms. Serum levels of Interleukin-33 (IL-33.) and STimulation expressed gene 2 (ST2) were quantified using enzyme immunoassay techniques. Additionally, the number of blood eosinophils, nasal eosinophils, Immunoglobulin E (IgE), and Secretory Immunoglobulin A (SIgA) were measured. Statistical analyses were conducted employing SPSS version 26.0 program. The diagnostic accuracy of the revised and simplified system was assessed using the receiver operating characteristic (ROC) curve. RESULTS: Throughout the study, we observed a significant reduction in the estimated total QoL score among children in both groups, with scores of 69.73 and 86.75 for the first and second groups, respectively, indicating a significant decrease decline in quality of life. A particularly critical criterion that exhibited a strong statistically significant correlation was the stress factor. Nearly 90% of patients in the second group, who are currently residing in conflict-affected areas, reported experiencing anxiety, which serves as a significant trigger for exacerbations. In our examination of the primary diagnostic criteria for the progression of SAR, we conducted a ROC analysis to assess the significance of predictors that may indicate an extreme allergic phenotype. These predictors included Visual Analogue Scale scores, blood eosinophil counts, nasal eosinophil levels, IgE, SIgA, IL-33, and ST2 levels. The analysis of potential prognostic factors allowed the creation of a practical algorithm for identifying patients at risk of developing an extreme allergic phenotype. This algorithm illustrates how our findings can be used to prognostically assess the severity of seasonal allergic rhinitis from a practical point of view. CONCLUSIONS: The conducted study identified the main diagnostic criteria that characterise the extreme allergic phenotype in children with SAR and determine the severity of its progression. Future research in this area will not only expand the existing diagnostic capabilities, but also contribute to the development of new treatment strategies for patients with allergic diseases.
Assessment of ventilation distribution in overweight and obese children with asthma using electric impedance tomography: a cross-sectional study.
Gambadauro A, Gambazza S, Manti S … +6 more , Lelii M, Madini B, Rocchi A, Andrenacci B, Chidini G, Patria MF
Ital J Pediatr · 2026 Mar · PMID 41888953 · Full text
BACKGROUND: Several studies have demonstrated an association between excessive body weight and asthma in children, underlining the link between obesity and resistance to treatments. The aim of this study is to investigat...
BACKGROUND: Several studies have demonstrated an association between excessive body weight and asthma in children, underlining the link between obesity and resistance to treatments. The aim of this study is to investigate the pattern of ventilation distribution and to assess the response to bronchodilator (BD) in a cohort of overweight/obese children with asthma, using standard spirometry and Electric Impedance Tomography (EIT). METHODS: Single-centre, cross-sectional study. Eligible children with asthma and excessive weight were enrolled during outpatient follow-up; EIT and spirometry were performed before and after the administration of 400 µg of inhaled salbutamol. RESULTS: A FEV1 < −1.64 z-score was found in 2/27 (7.4%) children (median age 12.4 yrs, 7 females); four children (14.8%) fulfilled the criteria for airway dysanapsis. Through EIT, a greater ventilation distribution was identified in the dorsal regions of the lungs. After BD, an increase in FEV1 z-score was observed, however, only 8/27 (29.6%) children reported a significant bronchodilation at spirometry; the median total %GI index and total %RVD40 remained unchanged, while a significant reduction in the VL %ROI was observed. No significant correlations were observed between pre-post BD differences in FEV1 z-score, %GI index, %RVD40 and anthropometric measures. CONCLUSION: Children with asthma and excessive weight had a peculiar pattern of regional ventilation distribution. BD administration generally resulted in a suboptimal spirometric response, with no significant changes in EIT measurements. The relatively limited response to BD could have several interpretations, and future studies are needed to better understand the mechanisms behind these findings.
A critical moment for neonatology: appeals from the Lancet Child & Adolescent Health Commission.
Dani C, Corsello G, De Luca D … +1 more , Agosti M
Ital J Pediatr · 2026 Mar · PMID 41888862 · Full text
BACKGROUND: The Lancet Child and Adolescent Health Committee on the Future of Neonatology has published an important document on the future of neonatology to highlight the significant challenges hindering the development...
BACKGROUND: The Lancet Child and Adolescent Health Committee on the Future of Neonatology has published an important document on the future of neonatology to highlight the significant challenges hindering the development of research in this field of medicine. MAIN BODY: The number of preclinical and clinical studies in neonatology is insufficient due to a lack of interest from industry and insufficient support from public agencies. In many countries, neonatology is not formally recognized as a medical specialty, which fosters a shortage of academic positions, with negative effects on both neonatology research and the training of young neonatologists. This situation is exacerbated by excessive bureaucracy, which hinders productive interaction with regulatory agencies and ethics committees and makes conducting randomized controlled clinical trials excessively expensive. The lack of shared standardized outcome definitions and the limited use of real-world data contribute to making neonatology research more difficult. CONCLUSION: We support the Commission’s proposal for a Global Alliance for Innovation in Neonatal Health (GAINH), which would include neonatologists, former patients, families, industry, and public bodies, such as governments and universities, to address and remove barriers to advancing neonatal health through high-impact research and innovation.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe