This research addresses the respiratory distress syndrome (RDS) in preterm newborns, caused by insufficient surfactant synthesis, which can lead to serious complications, including pneumothorax, pulmonary hypertension, and pulmonary hemorrhage, increasing the risk of a fatal outcome. By analyzing chest radiographs and blood gases, we specifically focus on the significant contributions of these parameters to the diagnosis and analysis of the recovery of patients with RDS. The study involved 32 preterm newborns, and the analysis of gas parameters before and after the administration of surfactants and inhalation corticosteroid therapy revealed statistically significant changes in values of parameters such as FiO2, pH, pCO2, HCO3 and BE (Sig.<0.05), ehile the pO2 parameter showed a potential change (Sig.=0.061). Parallel to this, the research emphasizes the development of a lung segmentation algorithm implemented in the MATLAB programming environment. The key steps of the algorithm include preprocessing, segmentation, and visualization for a more detailed understanding of the recovery dynamics after RDS. These algorithms have achieved promising results, with a global accuracy of 0.93±0.06, precision 0.81±0.16 and an F-score of 0.82±0.14. These results highlight the potential application of algorithms in the analysis and monitoring of recovery in newborns with RDS, also underscoring the need for further development of software solutions in medicine, particularly in neonatology, to enhance the diagnosis and treatment of preterm newborns with respiratory distress syndrome.

The purpose of this study was to explore and develop high-resolution infrared thermal (HRIT) imaging for screening toddler’s fracture. A Toddler’s fracture is a common tibial fracture of children younger than 6 years old. Initial x-ray radiographs may not show the fracture and another x-ray during a follow-on visit is usually required. The study included 39 participants admitted to an emergency department with a suspected toddler’s fracture. X-ray confirmed 8 cases with a toddler’s fracture (20.5%). Infrared images of participants were recorded on their index visit, focusing on region-of-interests on the injured and the contralateral (uninjured) legs. The uninjured leg acted as a thermal reference. Nine statistical measures were extracted from the images: maximum, mini-mum, mean, standard deviation, median, mode, interquartile range, skewness, and kurtosis. Wilcoxon rank sum test indicated that maximum, mean, standard deviation, median, and inter quartile range temperature measures were significantly different (p<0.05) when comparing fractured and non-fractured legs. Principal component analysis of these measures highlighted distinct separation of toddler’s fracture and non-fracture cases. Similarly, plots of the statistical measures further confirmed clustering of toddler’s fracture cases. The study demonstrated that HRIT imaging can be a valuable tool for screening for toddler’s fracture.

Background: COVID-19 is currently one of the most important medical challenges as it affects the entire population with children being infected as easily as adults. Objective: The study evaluated the mortality of under 17-year-olds and compare the frequency with that of adults in a cohort of 8986 COVID-19 positive patients hospitalized in a single care center. Design: retrospective clinical trial, all hospitalizations of COVID-19 positive patients as diagnosed by RT-qPCR were analyzed by revisiting their medical records. Setting: 8986 COVID-19 positive patients hospitalized in a Hospital de Base and the Infant and Maternal Hospital of São Jose do Rio Preto, SP, Brazil (HB/HCM) being these totals of 383 COVID-19 positive under 17-patients. Patients: patients COVID-19 positive under 17-year-olds were grouped by age and evaluated by analyzing their medical records. They were categorized as Group I, children, and adolescents under 19 years old and Group II, adults over 19 years. Results: Overall mortality in under 19-year-olds was 12 deaths, that is, 3.13% of the patients in this age group and 0.55% of the overall mortality from COVID-19. Mortality in the group of adults was 2197 equivalent to 24.45% of the hospitalized adults and 99.45% of overall deaths. Mortality was significantly higher for adults than for under 19-year olds (p-value < 0.0001). Regarding the different ages of children and adolescents, the number of deaths of under 1-year olds was 2/123 (1.62%), of 1-4 years it was 4/95 (2.11%), of 5-9 years it was 1/47 (2.13%), of 10-14 years it was 1/40 (2.5%) and of 15-19 years it was 4/78 (5.13%). There were no statistical differences between the different age groups ( p-value = 0.3). Conclusion: Mortality from COVID-19 in children and adolescents was lower than in adults and generally associated with other comorbidities with the main association being with heart disease.

Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children. Respiratory syncytial virus (RSV) is the most common causative agent, however other viruses can be the reason of the disease. We retrospectively reviewed the clinical features of infants aged less than 12 months referred to our Pediatric Units of Chivasso, Cirié and Ivrea for acute bronchiolitis requiring hospitalization over two consecutive bronchiolitis seasons. Patient-, disease- and treatment related variables were analyzed in this retrospective study. We were able to show how with the high flow oxygen support (HFNC) only a very low number of children (8 out of 192) need to be trasferred to our HUB referral centers. The probability of success were 96% for all patients and 93% for RSV vs. 98% for non-RSV patients (P=NS). Factor associated to failure of treatment were age below 1 months and the failure of HFNC. The wide and increasing use of HFNC in pediatric inpatients improved management of bronchiolitis in Spoke hospitals, reducing transfer to a Hub hospital provided with Intensive Care Units.

The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The children’s medical charts were analyzed to determine age, sex, anthropometric measurements, activity assessment using Hoffer’s scale and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the studied group compared with the reference group. A significant positive correlation between uL-FABP and proteinuria was found. Children with a history of vesicoureteral reflux (VUR) tended to have elevated uL-FABP. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and history of VUR may be the factors influencing uL-FABP.

Background: Pediatric ureteropelvic junction obstruction (UPJO) is a common urinary tract issue. Accurate assessment of postoperative kidney function is crucial for prognosis. Previous studies mainly focused on postoperative renal function and individual factors. Radionuclide imaging was costly and unsuitable for long-term follow-up. For aligning closely with clinical needs, we emphasizing renal morphology enhancement, and comprehensively analyzed factors influencing UPJO surgery outcomes. Methods: We retrospectively studied 150 pediatric UPJO patients (July 2012-July 2022) with severe anteroposterior renal pelvis dilation (APD grades 4-5) who underwent laparoscopic dismembered pyeloplasty. Demographics, symptoms, preoperative findings, and postoperative renal ultrasounds were assessed. We performed multivariable logistic regression analysis to identify significant predictors of prognosis and construct a regression model. Results: Among the 150 pediatric patients, 78 (52%) showed improvement in renal morphology after surgery. In the multivariate logistic regression analysis, age at surgery, duration of hydronephrosis, body weight, and preoperative creatinine were identified as significant prognostic factors for postoperative outcomes. The nomogram (AUC: 0.92) was constructed based on these factors and could serve as a useful tool for clinicians in evaluating the surgical prognosis of children with UPJO. Conclusions: This study reveals that among pediatric patients with severe hydronephrosis resulting from UPJO, those who are younger, have a shorter duration of illness, normal serum creatinine levels, and a healthy body weight tend to experience better postoperative recovery. This finding emphasizes the importance of adopting more proactive clinical interventions when managing such cases, with the goal of achieving enhanced recovery outcomes for affected children.

In the last two decades, the development of high-throughput diagnostic methods and availabil-ity of effective treatments has increased interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry dis-ease, Gaucher disease), using enzyme activity assay by tandem mass spectrometry, and bi-omarker quantification as second tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive pre-dictive value 40%), with an overall incidence of 1:4,874. Of these, 3 infantile-onset Pompe dis-ease, 2 neonatal-onset Gaucher disease and 4 mucopolysaccharidosis type I patients were imme-diately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrated the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient out-comes. Challenges such as false positive rates, the diagnosis of variants of uncertain significance or late-onset forms, and the lack of treatment for neuronopathic forms, should be addressed.

Preterm birth (PTB), a multi-causal syndrome, is one of the global epidemics. Maternal nutrition, but also neonatal and placental telomere length (TL), are among the factors affecting PTB risk. However, the exact relationship between these factors and the PTB outcome, remains obscure. The aim of this review, was to investigate the association between PTB, maternal nutrition and placental-infant TL. Observational studies were sought, with the keywords: maternal nutrition, placenta TL, newborn, TL, and PTB. No study was found that included all keywords simultaneously, and thus, the keywords, were searched in dyads, to reach assumptive conclusions. The findings show that maternal nutrition affects PTB risk, through its influence on maternal TL. On the other hand, maternal TL independently affects PTB risk, and at the same time PTB is a major determinant of offspring TL regulation. The strength of the associations and the extent of the influence from covariates, remains to be elucidated in future research. Furthermore, the question of whether maternal TL, is simply a biomarker of maternal nutritional status and PTB risk, or a causative factor of PTB, to date, remains to be answered.

Chronic non-bacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn's disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included non-steroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use, suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Abstract Background: Massive resection of the small intestine leading to short bowel syndrome (SBS) deprives organism of many immunocompetent cells concentrated in gut associated lymphoid tissue- the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, basing on peripheral lymphocyte subsets and serum immunoglobulins. Methods: 15 children, who underwent bowel resection in the first month of life and required further home parenteral nutrition were enrolled into the study.. Based on flow cytometry the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+and activated T cells. Results: Significantly statistical differences were found for the rates of lymphocytes B, T, CD8 + and NK cells. Absolute count of NK cells was lower in SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+ and percentages of lymphocytes CD4+, and activated T cells inversely correlated with the time after resection. Conclusions: Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time after resection points out the necessity for longer follow- up.

The field of human microbiome and gut microbial diversity research has witnessed a profound transformation, driven by advances in omics technologies. These advancements have unveiled essential connections between microbiome alterations and severe conditions, spurring the development of new frameworks through epidemiological studies. Traditionally, each individual was thought to harbor unique microbial communities acquired early in life, but recent research challenges this belief. The neonatal microbiome's onset, influenced by factors like delivery mode and maternal health, remains a subject of intense debate, hinting at potential intrauterine microbial processes. In-depth research reveals associations between microbiome profiles and specific health outcomes, ranging from obesity to neurodevelopmental disorders. Understanding these diverse microbiome profiles is essential for unraveling the intricate relationships between the microbiome and health outcomes.

Background: Acute viral gastroenteritis remains a leading cause of health care cost globally, prompting the need for basic diagnostic strategies. Objectives: This study aims to assess the impact of viral gastroenteritis on hemogram and C-reactive protein. Methods: By conducting a retrospective study, three groups of children diagnosed with gastroenteritis (rotavirus positive, adenovirus positive and rota/adenovirus negative group) were compared in terms of hemogram parameters and C- reactive protein. Results: Among 756 children with gastroenteritis, 7.9% of patients were rotavirus positive and 6.5% of them were adenovirus positive. Our findings disclosed a statistically significant association between low lymphocyte (2.2 ± 1.45) and MPV value (7.38 ± 0.4 fL) with rotavirus gastroenteritis. Also, the analysis revealed a high neutrophil/lymphocyte ratio (2.8± 2.1) in rotavirus group. However, our study did not reveal any prominent laboratory marker that serves as a distinctive feature of adenovirus unlike rotavirus. Conclusions: In conclusion our research highlights the potential of decreased mean platelet volume and lymphopenia as diagnostic markers for rotavirus gastroenteritis.

Early onset neonatal sepsis is a significant contributor to neonatal morbidity and mortality. Although blood cultures remain the diagnostic gold standard, they detect pathogens in only a minority of suspected cases. This study compared the accuracy of blood cultures with a rapid multiplex PCR test. Newborns at risk for neonatal sepsis were prospectively screened as recommended per national guidelines. Evaluations included laboratory parameters (CrP, IL6, differential blood count), blood culture, and a molecular multiplex PCR test (ROCHE LightCycler SeptiFast) identifying 20 common microbial agents. Blood samples were taken simultaneously from umbilical cord or venous sources on the first day of life. Of 229 infants included, 69% were born preterm. Blood culture and multiplex PCR sensitivity were 7.4% and 11.1% respectively. Specificity, negative and positive predictive values between methods showed no significant variance, though multiplex PCR had more false positives due to contamination. The limited sensitivity of blood cultures for early onset neonatal sepsis is concerning. Despite quicker results, multiplex PCR does not enhance diagnostic accuracy or antibiotic therapy guidance, thus it can not be recommended for this indication.

Objective: To explore the inflammatory markers for the development of obliterative bronchiolitis (OB) after adenovirus infection in children. Methods: In this retrospective study, the medical data of 62 children with adenovirus pneumonia treated in our hospital between February 2020 and November 2021 were collected and assigned to an OB group (n = 30) or non-OB group (n = 32) according to the presence of OB. Clinical characteristics of patients included gender, age, prematurity, underlying disease, length of hospitalization, type of adenovirus infection, ventilator use, length of ventilator use, and laboratory index levels. Results: Children with OB were associated with higher serum ferritin levels versus those without (P < 0.05). There were no significant differences in the immunoglobulin E (IgE), interleukin-6 (IL-6), partial arterial pressure of oxygen (PaO₂), D-dimer, lactate dehydrogenase (LDH), and lymphocyte absolute values between the two groups of children (P > 0.05). Logistic multifactorial regression analysis revealed that the length of ventilator use and serum ferritin level were inflammatory markers for the development of OB in children with adenovirus pneumonia. Conclusion: The length of ventilator use and serum ferritin levels are inflammatory markers for the development of OB after adenovirus infection in children, and timely measurement of the above indicators in children is instrumental in predicting the prognosis of children.

This randomized control trial aims to test the hypothesis that twice-daily nurse-administered saline enema(SE) is comparable to physician-administrated SE in very low birth weight infants (VLBW) with meconium obstruction of prematurity (MOP). MOP is defined as no bowel opening for 48 h, and treatment failure is defined as the need for additional intervention and safety. Twice-daily SE was administered by accredited nurses, surgeons/neonatologists using standardized protocols. The outcomes were comparability of nurse to physician-administered SE in terms of frequency of administration, catheter insertion length and volume of enema, daily maximum meconium output, and treatment failure, defined as the need for additional intervention. Safety outcomes were evaluated. Twenty-eight infants were managed with SE. 389 SE were administered, 96 and 293 in 750-999g and 1000-1500g birth weight groups, respectively. Nurses administered 72.9% and 81.5% of SE in 750-999g and 1000-1500g birth weight groups, respectively. Physicians performed the rest of the SE. Daily meconium output was comparable in nurse and physician-administered SE in both groups. There were no treatment failures or adverse events in both SE group. SE administered by nurses was found to be comparable in terms of safety, efficacy, and frequency of administration to that of physician-administered SE.

Background: Neonatal transportation of sick newborns is a major predictor of outcome. Prompt identification of the sickest newborns allows immediate corrective intervention and outcome optimization. Multiple severity scores were developed, however an optimal score has not yet been identified. Aim: To identify a rapid, accurate, and easy to perform score predictive for neonatal mortality in outborn neonates. Material and methods: All neonates, irrespective of gestational age, admitted by transfer in our level III regional neonatal unit between 01.01.2015 and 31.12.2021 were included. Infants with congenital critical abnormalities were excluded. Sick neonatal score (SNS) was calculated and compared between survivors and non-survivors. Gestational age (GA), birth weight (BW), gender, Apgar score, place of birth, time between delivery and admission (AT), early onset sepsis were collected from medical records and compared between study groups. Subgroup analysis was performed based on gestational age (preterm versus term infants). A new score was elaborated, including GA, BW, and AT, namely MSNS-AT score, to further improve mortality prediction. The main outcomes were mortality prediction using SNS and MSNS-AT score. Univariable and multivariable analysis, including Cox regression, were performed using SPSS Statistic 22.0. P-value was considered statistically significant if <0.05, 95% confidence intervals, odds ratio and hazard ratios were calculated were appropriate. Results: A total of 418 outborn infants were admitted during study period; 15 infants were excluded due to critical congenital defects. Out of 403 outborn infants, 217 born prematurely (53.8%), 224 males (55.6%), 20 died (4.96%). Compared to the survivors, the non-survivor neonates had significantly lower GA, BW, and SNS score (p<0.05), although only SNS score remained significantly lower in all subgroups (preterm vs term infants). A SNS score ≤8 was associated with mortality both in the whole study group and in subgroups (p<0.001). Time to admission was significantly associated with increased mortality rate in the whole group (p<0.05) and in preterm infants but not in term ones (p>0.05). In univariable and multivariable Cox regression models, MSNS-AT score, with a cut-off optimal value of ≤10 was more precise in predicting mortality compared to SNS (AUC 0.735 vs. 0.775) when applied to the entire group, had a lower accuracy in the term infants (AUC 0.765 vs 0.809) and a better accuracy the preterm infants group (AUC 0.885 vs. 0.810). Conclusions: The MSNS-AT score – calculated by adding GA, BW, and AT to the SNS score - significantly improved mortality prediction at admission in the whole study group as compared to SNS score. The best accuracy prediction of MSNS-AT score was observed in preterm infants suggesting that, besides GA and BW, TA may be decisive for the outcome of outborn preterm infants. Further studies are necessary to confirm the predictive value of MSNS-AT score and to identify variables that can improve its value in term infants without affecting the simplicity, ease, and rapidity of the scoring system.

Intense alterations of mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and represent an important cause of morbidity and decreased quality of life. These disor-ders have traditionally been defined as renal osteodystrophy and classified based on bone biop-sy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been difficult to adequately evaluate renal osteodystrophy in pe-diatric CKD. This has led to suboptimal management of bone disorders in children. CKD-mineral and bone disorder (CKD-MBD) is a new term used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances of cal-cium, phosphate, parathyroid hormone and vitamin D, bone abnormalities and soft tissue calci-fication. This literature review aims to explore the pathogenesis, diagnostic approach, and treat-ment of CKD-MBD in children and the specific consequences of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition.

Introduction. Congenital muscular torticollis (CMT) is an asymmetrical head positioning resulting from structural changes in the sternocleidomastoid muscle (SCM) that occurs early in a child’s development period or due to perinatal trauma. Children with CMT exhibit a marked imbalance in tension between the SCMs. When the clinical picture is typical, an ultrasound scan is performed to reveal characteristic lesions, such as tissue fibrosis or post-traumatic changes. Early diagnosis of CMT in newborns and implementation of treatment offer the chance of a complete cure. Torticollis treatment aims to rebuild the SCM's normal function by restoring its anatomical length, normal cervical spine mobility and muscle flexibility to enable regular head movements. Surgical treatment is performed when conservative methods fail to improve the patient’s condition. Indications for surgery include marked shortening of the SCM, persistent fibrosis in the muscle, constant head and facial asymmetry, and rotation or lateral flexion in the cervical spine restricted by > 15°. After hip dislocations and foot deformities, pediatric orthopedics addresses torticollis as the third most common congenital anomaly. Aim. This study was a retrospective analysis of 111 children diagnosed and treated due to CMT. Methods. The following were determined: the relationship between the side of CMT location and the type of delivery (cc vs. natural), between the body weight at birth and the side of CMT location, between the extent of SCM thickening and the type of delivery, and the incidence of CMT depending on the order of delivery. Results and conclusions. The analysis showed that CMT was more common in boys 61(54%) than in girls 51(46%), which may be related to the greater birth weight in boys. Of the pediatric patients with CMT, 76% were primiparous. More often, children born via natural delivery had left-sided torticollis with a more significant broadening of the SCM on ultrasound scans than right-sided torticollis. Theories of torticollis development pathophysiology should be deepened, systematized, and further researched.

Recombinant human erythropoietin (rhEPO) treatment is an alternative to erythrocyte transfusions in neonates with anemia of prematurity (AOP). This study assesses the impact of rhEPO administration within the first week of life on the incidence of AOP (any stage, individual AOP stages, and red-blood-cell (RBC) transfusions. Out of 108 preterm neonates, 49 were administered rhEPO and compared to the remaining group using univariate and multivariate analyses. Univariately, gestational age (GA), birth weight (BW), hemoglobin (Hb), hematocrit (HCT), and RBC levels, and iron administration were significantly associated to AOP (p&lt;0.05 each); however, only the latter remained significant after adjusting for covariates (AOR: 2.75, 95% CI, 1.06–7.11). Multinomial analysis revealed rhEOP therapy was associated with a near 3-fold reduction in moderate AOP incidence (OR: 0.36, 95% CI, 0.15–0.89). Furthermore, ANCOVA revealed positive correlations between rhEPO administration and 21-day Hb (p&lt;0.01), HCT (p&lt;0.05), and EPO (p&lt;0.001) levels. The results confirm previously reported benefits of rhEPO treatment, such as reduced moderate AOP incidence and increased Hb, HCT, and serum EPO levels.

Adenoviruses are associated with respiratory tract, gastrointestinal or, less frequently, other involvement. Epidemics of adenovirus infections occur globally, in communities and in closed or crowded settings. In our institution, an outbreak of Adenovirus infection in infants and children was recently observed. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n=67, cough n=44; tonsillar exudate n=17; other respiratory signs n=4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n=26, vomiting n=8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN and platelets, while CRP level approached statistical significance (p=0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, possible association between level of CRP and presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had significantly more often tonsillar exudate and diarrhea, while those in the lower tertile had a 4.4 days duration of fever, vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p=0.006). Duration of hospitalization was not associated with the CRP level. The median time from the receipt of positive adenovirus PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of adenovirus detected by PCR ranged between 47 million and 15/L. Falling in the highest terzile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception of a significantly higher leukocyte count. Rapid turn-around of results of molecular testing of adenovirus genome on pharyngeal swab allowed us to rapidly diagnose adenovirus infection, allowing stopping antibiotic therapy and immediate discharge, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of adenovirus from pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing preferential use of qualitative rather than quantitaive assay.

Autism spectrum disorder (ASD) is a common condition with lifelong implications and a strong hereditary component suggesting genetic underpinnings. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes not associated with ASD (P = 0.0002, odds ratio 29), validating that most are indeed disease related. Only 14/34 (41%) of PDV cases had the variant listed on the laboratory report, and reanalysis increased diagnostic yield from 28% to 68%. Variants that we assigned as PDVs yet not on the report were predominately de novo in genes not yet reported as ASD associated. Many subjects both with and without a PDV had inherited Qualifying variants in known ASD-associated genes, suggesting polygenic inheritance. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

Suboptimal micronutrient intake in children remains a public health concern around the world. This study examined the relationship between a previously defined dietary carbohydrate quality index (CQI) and the risk of micronutrient intake inadequacy in a pediatric cohort of Spanish preschoolers. Children aged 4-5 years old were recruited at their medical center or at school, and information on sociodemographic, dietary, and life-style variables were collected through a self-administered online questionnaire. Dietary information was obtained from a validated 147-item semi-quantitative food frequency questionnaire. We calculated the CQI and categorized participants in quartiles according to their score. We assessed the intakes of 20 micronutrients and evaluated the probability of intake inadequacy using the Estimated Average Requirement cut-off point. Generalized estimating equations were used to adjust for potential confounders and account for the intra-cluster correlations between siblings. The adjusted proportions of children with inadequate intake of ≥3 micronutrients were 23%, 12%, 11% and 9% in the first, second, third and fourth quartiles of the CQI, respectively. Children in the highest quartile of CQI had 0.22-fold lower odds (95%CI 0.10-0.48) of having ≥3 inadequate micronutrient intakes than their peers in the lowest quartile. These findings reinforce the relevance of carbohydrate quality in children’s diets.

Introduction: Obstructive Sleep Apnea (OSA) is a respiratory condition identified by the partial or complete obstruction of the upper air passages during sleep. These episodes can lead to complications in neurobehavioral and cognitive domains and cardiovascular issues, especially in children. The involvement of OSA in ocular health during adulthood has been reported, but it remains a topic of debate in pediatric cases. Objective: This review aims to analyze the correlation between OSAS and ocular health in children. Specifically, it investigates the effects of OSA on ocular structures and conditions and explores potential improvements through treatment. Subjects and Methods: The research employed three search engines: PUBMED/MEDLINE, SCOPUS, and WebOfScience. After initial identification, 120 irrelevant articles were excluded. Of these, 10 pertained to the adult population, and 110 focused on the pediatric population. Following a careful selection process and the application of enrollment criteria, six relevant articles were included, all in English, focusing on the effects of OSA on children's eyes. Among these, three studies explored correlations with choroidal alterations, while three investigated retinal and optic nerve changes. Two studies analyzed post-otorhinolaryngological intervention ocular changes. Results: OSA leads to increased intraocular pressure and reduced optic nerve thickness in adults, but treatment alleviates this condition. An immediate correlation between OSA and optic nerve thickness in children does not readily emerge, although age appears to play a role. Pediatric patients with OSA exhibit corneal anomalies and an increase in optic nerve thickness, possibly due to intermittent hypoxia. Studies indicate that OSA can influence retinal vascular density in children, with an increase observed after treatment and reduced choroidal thickness in cases of adenotonsillar hypertrophy. Conclusion: This literature review has highlighted how OSA in children can significantly impact ocular health, with observed alterations in the optic nerve, choroid, retina, and cornea. While the direct correlation with the optic nerve may not always be evident, OSA can elevate intraocular pressure and lead to structural changes. However, treatment appears to bring about improvements. The necessity for regular monitoring to detect potential adverse effects underscores the importance of promptly addressing childhood OSA.

Objective Our objective was to observe the benefits and limitations of WES (Whole Exome Sequencing) in the prenatal setting, in the Romanian population. The scope was to observe the diagnostic yield in comparison to molecular karyotyping testing, which had negative results, as well as a case of consanguinity. Methods The first criteria was selecting pregnancies with abnormal ultrasound findings. These findings would not lead the medical team to a certain known syndrome. Second, we performed SNP-array, which tested negative in all cases, except for Case number 9 which had an abnormal result. The ulterior testing method was WES, using Massive Parallel Sequencing of the whole coding region of the human genome on Next Generation Sequencing Platform, NovaSeq 6000 (average coverage >100X, read length: 2x100bp). The Twist Human Core Exome kit RefSeq & Mitochondrial panel (Twist Bioscience) was used for the library preparation. Bioinformatic analysis was performed by direct comparison of the genome of the test sample with the human reference sequence (hg38). Results Our small cohort of 10 patients, resulted in a 50% diagnostic yield. After receiving the results whether a diagnose or a negative result, 2 couples chose to terminate the pregnancy, 5 were born affirmatively without symptoms, and are still monitored up to date. One of the pregnancies led to a stillbirth. We have also found 3 incidental findings that helped the multidisciplinary team better manage the patient as well as the members at risk. Conclusion In this article we present 10 cases which were tested through prenatal WES, showing the great diagnostic yield in comparison to SNP-array in our selected cases. As a closing remark, we wish to highlight the benefits of WES testing in prenatal cases. Further testing is needed to get a clearer picture of the prenatal diagnostic yield in the Romanian population.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is one of the most controversial diseases in pediatric rheumatology. Despite its first description being published more than 25 years ago as the sudden and rapid onset of obsessive-compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine re-lease in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

Low 25 OH vitamin D (25(OH)D) in preterm infants is a risk factor of bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and lung histological alterations evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120nmol/L is also a risk factor for BPD or death. This retrospective single-center cohort study included all infants born <31 weeks gestational age without major malformation with at least a determination of 25(OH)D <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120nmol/L (50.5% vs 43.9%, p=0.53). The logistic regression identified weight (OR 0.997, 95%CI [0.995-0.998]) and term (OR 0.737, 95%CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95%CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

In the continued battle against one of the oldest enemies known to mankind, Mycobacterium tuberculosis (MTB), the emergence of drug resistance among children poses multiple challenges for early detection and treatment. Molecular diagnostics and newer drugs like bedaquiline and delamanid have strengthened the armamentarium and helped design convenient, safe and child-friendly therapeutic regimens against drug-resistant tuberculosis (TB). Preventive strategies like treatment of TB infection among children living in close contact with patients with drug-resistant TB and effective vaccines against TB are currently in the investigative stages of development and implementation. In addition to the implementation of recent novel diagnostics and treatment modalities, effective psychosocial and nutritional support, as well as dedicated monitoring for compliance and adverse effects, are crucial determinants for successful treatment outcomes in these children.

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD, due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive cure available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cells-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to higher-risk subpopulations of premature infants. Hence the need for easy-to-use noninvasive tools for a standardized, precise and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).

Coronavirus disease (COVID-19) and its outcomes remain one of the most challenging problems today. COVID-19 in children could be asymptomatic but can result in a fatal outcome, therefore, prediction of the disease severity is important. The goal was to investigate the human genetic factors that could be associated with COVID-19 severity in children. Single nucleotide polymor-phisms of the following genes were studied: ACE2 (rs2074192), IFNAR2 (rs2236757), TYK2 (rs2304256), OAS1 (rs10774671), OAS3 (rs10735079), CD40 (rs4813003), FCGR2A (rs1801274) and CASP3 (rs113420705). In the case-control study were 30 children with mild or moderate course of the disease; 30 with severe COVID-19 symptoms and multisystem inflammatory syndrome in children (MIS -C) and 15 healthy who did not have COVID-19 infection (PCR negative, Ig G negative). The study revealed that ACE2 rs2074192 (allele T), IFNAR2 rs2236757 (allele A), OAS1 rs10774671 (allele A), CD40 rs4813003 (allele C), CASP3 rs113420705 (allele C) and male sex contribute to severe course COVID-19 infection, and MIS-C in 85.6% of cases. The World Health Organization reported new COVID-19 variants may cause previously unseen symptoms in chil-dren. Although the study has limitation due to cohort size, the findings can help provide a better understanding of SARS-CoV-2 infection and proactive pediatric patient management.

Introduction: Determination of radiological bone age (BA) is a diagnostic method that consists of estimating chronological age (CA) from the bone maturation of children. Although environmental and hormonal factors can interfere with bone ossification, the process is essentially dependent on ancestral inheritance. These ethnic backgrounds are not usually considered, which can lead to biased interpretations and inadequate decision-making by pediatricians or forensic experts. The objective of this study was to determine the precision and accuracy of these radiological procedures among different ethnic groups. Methods: A qualitative systematic review carried out following MOOSE statement and previously registered in the International Prospective Registry of Systematic Reviews PROSPERO (CRD42023449512). Search was performed in MEDLINE (PubMed) (n=561), Cochrane Library (n=261), CINAHL (n=103), Web of Science (WOS) (n=181) and public institutional repositories (n=37) from inception to 31st December 2022 using Mesh as “Diagnostic Techniques and Procedures”, “Diagnostic imaging”, “Radiography”, “Age Determination by Skeleton” and free terms combining with booleans “AND” and “OR”. PEDro scale, and Risk of Bias in non-randomized Studies of Exposure (ROBINS-E) were used to assess methodological quality and risk of bias of included studies respectively. Results: 51 articles (n=19,531) were included according to the inclusion criteria previously established. There was a good to moderate methodological quality and a high to very high risk of bias. Skeletal methods for determining BA were precised in terms of intra-observer and inter-observer reliability in all ethnic groups. Regarding to accuracy of Skeletal methods in Caucasians and Hispanic children, GPA was accurate at all ages, but in youths, TW3 RUS could be a consistent alternative. In Asian and Arab, GPA and TW3 overestimated BA in adolescents near adulthood. In African youths, GPA overestimated BA while TW3 was more accurate in estimating CA. Dental and Cervical radiographic methods are equally precise but lesser accurate than Skeletal BA determination. Conclusion: Skeletal radiographic methods GPA and TW3 are both precise for BA determination among all ethnical groups, but their accuracy in estimating CA can be altered by racial bias.

Puberty identifies the transition from childhood to adulthood. It normally lasts from 3 to 5 years and begins from 9 years in males and 8 years in females, although with differences related to familiarity and geographical origin. Precocious puberty is the onset of signs of pubertal development before age 8 in girls and before age 9 in boys, it has an incidence of 1/5000–1/10.000 with an F:M ratio ranging from 3:1 to 20:1. Based on the mechanism that triggers puberty, precocious puberty can be classified as central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also known as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual characteristics, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analogs therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.

Acute myeloid leukemia (AML) is the second common hematologic malignancy in children. The incidence of childhood AML is much lower than acute lymphoblastic leukemia (ALL), which makes the childhood AML a rare disease in children. The role of genetic abnormalities in AML classification, management and prognosis prediction is much more important than before. The WHO classification of myeloid neoplasms and the European LeukemiaNet (ELN) classification were both revised in 2022. The application of the new information in childhood AML will be upcoming in the next few years. The frequency of each genetic abnormality in adult and childhood AML is different, therefore, in this review we emphasize in well-known genetic subtypes in childhood AML, including Core-binding factor AML (CBF AML), KMT2Ar (KMT2A/11q23 rearrangement) AML, normal karyotypes AML with somatic mutations, unbalanced cytogenetic abnormalities AML, NUP98 11p15/NUP09 rearrangement AML and acute promyelocytic leukemia (APL). Current risk group classification, management algorithm in childhood AML and novel treatment modalities, such as targeted therapy, immune therapy, chimeric antigen receptor (CAR) T-cell therapy are reviewed. Finally, the indications of hematopoietic stem cell transplantation (HSCT) in AML are discussed.

Kinetic estimation of glomerular filtration rate (KeGFR) proved its utility in predicting acute kidney injury (AKI) in both adults and children. Our objective is to assess the clinical utility of KeGFR in predicting AKI severity and progression to acute kidney disease (AKD) in patients already diagnosed with AKI and to examine major adverse kidney events at 30 days (MAKE30). We retrospectively calculated the KeGFR in the first 24 hours of identified AKI (KeGFR1) and in the 24 hours prior to AKD (KeGFR2) in all admitted children under 18 years old. The cohort consisted of 803 patients with AKI. We proposed a new classification of KeGFR stages, from 1 to 5, and assessed the predictive value of KeGFR stages for AKD development and MAKE30. AKI severity was associated with lower KeGFRs. KeGFR1 and KeGFR2 predicted AKD with AUC values between 0.777 and 0.841 respectively, p<0.001. KeGFR2 had the best performance in predicting MAKE30 (AUC of 0.819) with a sensitivity of 66.67% and specificity 87.7%. KeGFR1 stage 3, 4 and 5 increased the risk of AKD by 3.07, 6.56 and 28.07 times respectively while KeGFR2 stage 2, 3, 4 and 5 increased the risk of AKD 2.79, 3.58, 32.75 and 80.14 times fold. Stage 5 KeGFR1 and KeGFR2 stages 3, 4 and 5 increased the risk of MAKE30 by 7.77, 4.23. 5.89 and 69.42 times in the adjusted models. KeGFR proved to be a useful tool in AKI settings. KeGFR dynamics can predict AKI severity, duration and outcomes.

Successful implementation of antibiotic stewardship programs (ASP) requires a well-structured approach involving all stakeholders. Despite embracing key responsibilities, nurses’ role remains poorly defined, preventing consistent engagement. We conducted a scoping survey to assess knowledge, attitude and perception of nurses towards nurse-led initial sepsis risk evaluation using the sepsis risk calculator (SRC) of newborns admitted to the mother-baby unit. Single-center, cross-sectional study. Study link was sent to all full-time nurses in mother-baby unit. Survey centered around knowledge of unit’s ASP and attitude and perception towards nurse-led initial sepsis risk evaluation. 89% response rate. 100% agreed that SRC reduced antibiotic use and 66% felt nurse-led sepsis risk evaluation will enhance nurse involvement, but this was offset by extra burden of work (66%) and low confidence in differentiating stable from clinically unstable infants (46%). Other facilitating factors included greater nurse/patient ratio (100%), targeted education (89%) and incorporation of the SRC into EMR (78%). Only 11% were willing to serve as champions for it. There was no significant correlation to age or experience however, greater number of fresh grads were interested in championing this effort. Our study identifies a need for strong foundation of knowledge and greater nurse/patient ratio as two main factors for improving nurse-led use of the SRC. Multi-site studies scoping barriers to nursing involvement for successful implementation of ASPs are necessary.

Background: It is known that Preeclampsia affects the lactogenesis. However, data on effects of this pathology on the human milk neurobiomarkers composition are not available. The aim of this study is to investigate the effects of this gestational pathology on Activin A levels, a neurobi-omarker known to play an important role in the development and protection of the central nerv-ous system. Methods: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an ELISA test. To investigate the effect of Preeclampsia on the Activin A concentration in the 3 lactation phases, mixed linear model with unistructural covariance structure, mother as random effect, and fixed effects were performed. Results: Activin A was detected in all samples. There were no significant differences between Preeclamptic and Normotensive women. The only significant effect is related to the lactation phase: it is significant the difference between colostrum and mature milk (p<0.01). In conclusion these results allow us to affirm that breast milk beneficial properties are maintained even if preeclampsia occurs.

This study aimed evaluating 7 years’ outcome in 118 very preterm newborn (VPN, gestational age=26±1.4wks) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS) requiring ventilation for 14±2 days post-natal age (PNA). Repeated instillation of 200mg/kg Poractant alfa (SURF) did not improve early bronchopulmonary dysplasia, but SURF infants needed less re-hospitalization than controls for respiratory problem at 1- and 2-years PNA. There was no growth difference at 7.1±0.3 years for 41 SURF vs. 36 controls (80% eligible children); 7.9% SURF vs. 28.6% controls presented asthma (p=0.021). Children underwent cogni-tive assessment (WISC IV) and pulmonary function testing (PFT) measuring spirometry, lung volumes and airway resistance. Spirometry showed differences (p<0.05) between SURF and con-trols (mean±standard deviation (median z-score)) for FEV1 (L/s) (1.188±0.690(-0.803) vs. 1.080±0.243(-1.446)); FEV1 after betamimetics (1.244±0.183(-0.525) vs. 1.091±0.209(-1.342)); FVC (L) (1.402±0.217 (-0.406) vs. 1.265±0.267(-1.141)), and FVC after betamimetics 1.452±0.237 (-0.241) vs. 1.279±0.264(-1.020)). PFT showed no difference in volumes or airway resistance. Global IQ median [Inter-quartile Range] was 89[82:99] vs. 89[76:98] with 61% children >85 in both groups. Former VPN presenting severe neonatal RDS treated with repeated Surfactant have improved lung function and less asthma at 7 years PNA. There were no differences in neurodevelopmental outcome

The 2022-2023 influenza season in Romania was characterized by high pediatric hospitalization rates, predominated by influenza A subtypes H1N1 and H3N2. Lowered population immunity to influenza after the SARS-CoV-2 pandemic and subsequent stoppage of influenza circulation, particularly in children who had limited pre-pandemic exposures, influenced hospitalization among children immunosuppressed, and patients with concurrent medical conditions who are at increased risk for developing severe forms of influenza. This study focused on the characteristics of influenza issues among paediatric patients, as well as the relationship between different influenza virus types and viral and bacterial coinfections and illness severity in the 2022-2023 season after the SARS-CoV-2 pandemic. We conducted a retrospective clinical analysis on 301 cases of influenza in pediatric inpatients (age ≤ 18 years), hospitalized at the National Institute of Infectious Diseases "Prof. Dr. Matei Balș" IX Pediatric Infectious Diseases Clinical Section between October 2022 and February 2023. The most significant age group was 57.8% representing children between one to four years old and female. The average clinical forms were found in 61.7%, whereas severe versions represented 18.2% of cases. Most of the complications were respiratory (acute interstitial pneumonia, 76.1%), hematological (72.1%), represented by intra-infectious and deficiency anemia, leukopenia, thrombocytopenia), 33.6% were digestive, such as diarrheal disease, liver cytolysis syndrome, and the acute dehydration syndrome associated with electrolyte imbalance (71.4%). Severe complications were associated with a risk of unfavorable evolution: acute respiratory failure and neurological complications (convulsions, encephalitis). No deaths were reported. We noticed that the flu season 2022-2023 was characterized by the association of co-infections (viral, bacterial, fungal and parasitic) more frequent than in previous years (26.2% vs. 16%), which evolved more severely, with prolonged hospitalization and more complications (p<0.05), and time of use of oxygen therapy was statistically significant (p > 0.05); influenza vaccination in this group was zero. In conclusion, coinfections with respiratory viruses increase the severity of the pediatric population's immunity to influenza, especially among young children who are more vulnerable to developing a serious illness. All people above the age of six months should get vaccinated against influenza to prevent the illness and its severe complications.

Three-quarters of a million babies are born extremely preterm (< 28 weeks’ gestation) world-wide with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopul-monary dysplasia (BPD) and 10% suffer from cerebral palsy. Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) agonist, may reduce the incidence of BPD and improve neurodevelopment in extreme preterm babies. Pioglitazone exerts an anti-inflammatory action mediated through Nuclear Factor-kappa B repression. PPARγ signalling is underactive in preterm babies as adiponectin remains low during the neonatal pe-riod. In newborn animal models, pioglitazone is shown to be protective against BPD, necrotising en-terocolitis, and lipopolysaccharide-induced brain injury. Single Nucleotide Polymorphisms of PPARγ are associated with inhibited preterm brain development and impaired neurodevelop-ment. Pioglitazone was well tolerated by the foetus in reproductive toxicology experiments. Bladder cancer, bone fractures, and macular oedema seen rarely in adults may be avoided with a short treatment course. Other effects of pioglitazone including improved glycaemic control and lipid metabolism may provide added benefit in prematurity. Currently, there is no formulation of pioglitazone suited for administration to preterm babies A liquid formulation of pioglitazone needs to be developed before clinical trials. The potential benefits are likely to outweigh any anticipated safety concerns.

Background. Human Milk (HM) is a dynamic nourishment: its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important evaluate the impact that gestational diseases have on HM components and if their presence, as source of oxidative stress in the mother, influence milk’s redox homeostasis. To assess Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) effect on milk’s total oxidative load, we chose to investigate both oxidative and antioxidant aspects, with respectively Lipid hydrop-eroxides (LOOHs) and Glutathione (GSH)). Methods. GSH and LOOHs were quantified using an ELISA test. To investigate the effect of pathology on redox homeostasis, mixed linear model with unistructural covariance structure was performed. Results. A total of 120 mothers were re-cruited. The GSH concentration results significant lower in GDM women than in healthy only in colostrum (p<0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. Discussion. Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the anti-oxidant composition of HM mainly in colostrum, but in case of PE, the composition of HM milk is preserved.

Sleep-disordered breathing is a significant problem affecting the pediatric population. These conditions can affect sleep quality and significantly affect children's overall health and well-being. Difficulties in social interaction, communication, and repetitive behavioral patterns characterize autism spectrum disorder. Sleep disturbances are common in children with ASD. This literature review aims to gather and analyze available studies on the relationship between SDB and children with autism spectrum disorder. We comprehensively searched the literature using major search engines (PubMed, Scopus, and Web of Science). After removing duplicates, we extracted a total of 96 records. We selected 19 studies for inclusion after a thorough title and abstract screening process. A total of 7 articles were ultimately included. This review has analyzed the relationship between autism spectrum disorder and sleep-disordered breathing, particularly Obstructive Sleep Apnea, highlighting an intriguing web of complex associations. Some studies involving children have demonstrated a significant association between autism spectrum disorder and the presence of Obstructive Sleep Apnea. Furthermore, a heightened risk of developing sleep disturbances, including sleep-disordered breathing, has emerged in children with autism. The risk and prevalence of obesity are increasing in pediatric subjects with autism spectrum disorder. Obesity has been identified as a predictive factor for Sleep-disordered breathing, and Body Mass Index can directly correlate with Obstructive Sleep Apnea in these children. Adenotonsillectomy has proven to be pivotal in improving behavioral issues in autism spectrum disorder children with obstructive Sleep Apnea. In conclusion, this review underscores the complexity of the interplay between autism spectrum disorder and sleep-disordered breathing, emphasizing the importance of further research to understand underlying mechanisms and develop optimal therapeutic and preventative approaches to enhance sleep quality and overall health in children with autism spectrum disorder.

Abstract: Background: Neonatal sepsis continues to be one of the leading causes of mortality and morbidity, particularly in under development and underdeveloped countries. We aim to compare laboratory parameters between the early-onset sepsis (EOS) and non-EOS groups and to evaluate the association between TLR2- Arg753Gln, TLR4 -Asp299Gly, IL6-174G/C and IL10-1082G/A gene single nucleotide polymorphisms and EOS susceptibility in preterm newborns. Methods: Genotyping of the TLR2, TLR4, IL6 and IL10 polymorphisms was performed in 36 preterm neonates by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). Logistic regression analysis was used to test the associations between the studied gene polymorphisms and EOS susceptibility. Results: Statistically significant differences in gestational age and birth weight were observed between the two groups, preterm neonates with EOS having a lower mean of gestational age (weeks, 29.4 ± 2.8 versus 32.6 ± 1.1, p = 0.00002) and lower mean of birth weight (gr., 1342.1 ± 446.5 vs. 1984 ± 376.9) than preterm neonates without EOS. C-reactive protein (CRP) values measured at first day significantly increased in EOS group compared with non-EOS group (median, 95% CI: 0.80 [0.40, 1.15] versus 0.30 [0.02, 0.50]). Mean of neutrophils significantly decreased in the EOS preterm neonates (mean difference: 17.3%, 95% CI: [4.0%, 30.5%], p = 0.0126) and non-EOS group (mean difference: 20.8%, 95% CI: [1.8%, 39.9%, p = 0.0354) between the first day and 7th hospitalization day. The minor IL10-A1082 allele frequency was higher in the EOS group than in the nonEOS group (50% versus 25%) with a marginal statistical significance (p=0.0550). In the dominant model, the A/G + A/A variant genotype of IL10- 1082G/A polymorphism significantly increased the odds of EOS compared with GG genotype (OR= 5.25, p = 0.0322). Conclusions: The results of the current study suggests the IL10- 1082G/A gene polymorphism as significant risk factor for early onset sepsis development in preterm neonates.

Lipofibromatous hamartoma, first reported in 1953, is a rare, slowly-progressive soft tissue tumor, characteristics of which include enlargement of the affected nerve by epineurial and perineurial proliferation of adipose and fibrous tissues. Out of previously reported 200 cases of lipofibromatous hamartoma of the median nerve, there have been approximately 40 pediatric cases under the age of 18. Herein, we report a case of lipofibromatous hamatoma of the median nerve in a 3-year-old female patient, who was surgically decompressed by carpal tunnel release only and histologically confirmed. The patient was followed-up on outpatient clinic basis annually along with ultrasonography, and the postoperative 10th year follow-up did not show recurrence or any deficits in motor and sensory functions

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nasal nitric oxide measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF) based on the latest literature. CONCLUSION: nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis, acute and chronic rhinosinusitis.

Children with history of prematurity are at higher risk of complications, comorbidities and iron deficiency. In this study we assess the prevalence of restless sleep disorder, as well as that of periodic leg movements during sleep (PLMS) in these children. Retrospective chart review of sleep studies in children aged 1-18 years, with history of prematurity. Only diagnostic studies in children without diagnosis of a genetic syndrome or airway surgery or tracheostomy were included. Three groups were compared, children with PLMS index&gt;5, children with restless sleep disorder (RSD), and children with neither elevated PLMS index nor RSD. During the study, 2,577 sleep studies were conducted. Ninety-two studies fit our criteria and were included in analysis. Median birth age was 31 weeks, interquartile range (IQR) 27-34 weeks. Thirty-two (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring; after polysomnography 18% were found to have PLMS index &gt;5/hour, 14% fit the criteria for RSD. There were no statistically significant differences in polysomnographic parameters between the children with RSD, PLMS and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p=0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5), or than in the nonRSD/nonPLMS group (median 2.0, IQR 0.8-4.5). There was elevated frequency of RSD and elevated PLMS in children with history of prematurity that might be linked to the increased risk of iron deficiency in premature infants. These new results add new knowledge on the prevalence of RSD in these children.

To learn what mothers know on newborn bloodspot screening (NBS), the procedure, and sources used, a pilot study was performed. An online questionnaire was developed, with a first part fo-cused on characteristics and the NBS procedure, a second on knowledge, information sources, and health care providers (HCP). This questionnaire was accessible until 200 answers were received. Characteristics of respondents were representative for the population. Mothers recalled verbal consent in 69.5%, 12.5% did not, 18% stated that no consent was requested. The ‘knowledge’ part contained 12 closed questions, 5 multiple-choice questions on sources, and assessment (5-point Likert) of the information transfer. The mean knowledge level was 7.2/12. Screening concepts (consequences, likelihood, sensitivity, carrier) and absence of notification of normal findings were well known. The fact that NBS is not compulsory and post-analysis sample handling were poorly known. Key HCPs were midwifes (80.5%) and nurses (38.5%). When the leaflet (44%) was pro-vided, the majority read it. Mean Likert scores were 3.36, 3.38, 3.11 and 3.35 (clarity, timing ap-propriateness, sufficiency, usefulness). The knowledge level and consent practices were reasonable well. Key HCP were midwives and nurses, leaflets were supporting. This should enable a quality improvement program to a sustainable NBS program in Flanders.

Standardized protocols were specifically designed and developed for clinical information collection and obtaining trio genomic information from infants affected with congenital anomalies (CA) and their parents, as well as securing human biological resources. Two large areas of these protocols include clinical and genomic information collection on CA which were difficult to diagnose using pre-existing screening methods. The following are three essential items for the clinical information collection protocol: establishment of a consent system for collecting and utilizing research resources, establishment of criteria for target patient selection, and collection of clinical and epidemiological information. A total of 138 cases consisting of 45 families of infants with CA and their parent trios have provided human-derived resources and genomic information. Whole genome sequencing data have been generated for all participants, and standardized protocols for resource collection and manufacturing have been developed. Phenotype information according to the Human Phenotype Ontology term and major test findings were recorded. It is important to keep updating and recording clinical symptoms and genetic diagnosis that are newly added or changed over time. The unique significance of this study is to develop a protocol that enables long-term tracking by adding growth and development tests that reflect important characteristics of newborns. By using these clinical and genetic information collection protocols for CA, it will be possible to establish an essential platform for early genetic diagnosis and diagnostic research, and further present new genetic diagnostic guidelines in the near future.

product transfusions, but clinical practices vary widely. Many very low birth weight (VLBW) infants receive packed red blood cell (RBC) or platelet transfusions during their initial NICU stay, with incidence inversely proportional to gestational age at birth ^1,2. Many critically ill infants are also transfused with plasma or cryoprecipitate to promote coagulation ^3,4. These blood product transfusions are most often prophylactic, with clinical decisions made in response to numerical blood count values, as opposed to therapeutic transfusions in the context of active bleeding.Emerging evidence has shown that some transfusion practices are harmful for certain NICU patients, such as platelet transfusions in preterm infants ^5,6. More broadly, transfusion reactions can occur with virtually all blood products ⁷ and these reactions are likely under-diagnosed, under-estimated, and under-reported in pediatric patients ³. Our intention was to establish optimal transfusion guidelines for our division and neonatal network, including 19 hospitals, based on a review of currently available literature.

Introduction: Mucopolysaccharidosis type I (MPSI) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and nonspecific symptoms resulting in high morbidity and mortality. The incidence of MPSI in US is estimated to be 0.26:100,000, however, it is unknown in Kuwait. This pilot study was undertaken to screen MPSI in all Kuwaiti neonates born at Farwaniya Hospital over a period of 12-months. This study examined the incidence of MPSI in a major center in Kuwait for inclusion in the national newborn screening program to enable its early detection and adequate treatment. Methods: All Kuwaiti neonates born at Farwaniya Hospital, Kuwait from December 2021 to December 2022, were screened for MPSI. The screening consisted of determining IDUA enzyme activity in dried blood spots (DBS)-derived samples by Tandem Mass Spectrometry. A follow-up genetic analysis of IDUA gene is planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. Results: A total of 618 newborns, including 331 (54%) males and 287 (46%) females, were screened. Twenty of them had deficient IDUA enzyme activity but showed negative genetic testing for IDUA. However, we have diagnosed one additional female baby with MPSI, who belonged to Farwaniya Hospital, but the parents chose to deliver in a private hospital. She presented at age three months with recurrent upper airway infections, snoring and extensive Mongolian spots. The molecular study revealed previously reported pathogenic nonsense variant in IDUA c.1882C>T; p.(Arg628Ter), associated with severe phenotype. That being included, MPSI is estimated to be about 0.3% among tested females and 0.2% of all screened cases in Kuwait. Conclusion: Our study is the first to evaluate the incidence of MPSI in Kuwait. Given the single center, small number of screened babies and the short study duration thus far, it is premature to calculate the incidence of MPSI. It is anticipated that as the study continues and more infants are examined, we would be able to estimate the incidence of this disease in our population correctly. Further studies including screening newborns in all maternity hospitals in Kuwait are needed to calculate the actual incidence of MPSI. Our data supports including MPSI in national newborn screening program to allow early initiation of treatment and thus improve disease outcome.

Introduction: congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of urinary collecting system, known as hydronephrosis or ureterohy-dronephrosis. Mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin 11 and TGFβ levels in obstructed ureteral tissue. The aim of the study is to investigate expression of fibrosis related genes in obstructive and normal ureteral tissue. Material and methods: it is a monocentric study in which nineteen patients were selected prospec-tively. 17 patients of which underwent Hynes-Anderson pyeloplasty due to the PUJO, 2 patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO) and 6 patients were chosen for control group: 5 underwent nephrectomies due to the kidney tumor and 1- upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR to evaluate the relative expres-sion of Tgfb1, Mmp1, Timp1, Pai1, Ctgf and Vegfa was performed. Expression levels of Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and Wilcoxon rank-sum test was performed to determine statistical significance of the differences. Results: significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, Pai1 was found. Discussion and conclusions: These findings suggest that tissue fibrosis similar to other tissues and organs is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF ex-pression is indicative of developmental origin of obstruction.

The aim of this study was to determine the potential of early inflammatory markers to diagnose late-onset neonatal sepsis - procalcitonin (PCT), interleukin 6 (IL-6), interleukin 8 (IL-8) and endocan (ESM-1), and to compare them with routinely used markers. A prospective (January, 2022 – January, 2023) clinical-epidemiological study was conducted in a third level NICU in Pleven, Bulgaria. Patients with suspected nosocomial infection and healthy controls were tested. A sandwich ELISA method was used to measure the serum concentrations. Sixty newborns with an average gestational age of 29.75 ± 3.61 gestational weeks were included, of which 35 % were symptomatic and infected, 33.3 % were symptomatic but uninfected, and 31.7 % were asymptomatic controls. The mean values of PCT, IL-6, I:T index and PLT differ significantly in the three groups. For ESM-1, IL-8 and CRP, the difference was statistically insignificant. The best sensitivity (78%) and negative predictive value (84%) was found for IL-6. The combination of PCT + IL-6 + I:T+ PLT demonstrated high precision (78%) and best sensitivity (94%) and negative predictive value (95%). The introduction into routine practice of indicators such as PCT and IL-6 may provide an opportunity to promptly optimize the diagnostic and therapeutic approach to LOS.

Since first described by Dr. Tomisaku Kawasaki in 1967, the clinical diagnosis of Kawasaki disease (KD) has remained relatively unchanged. However, studies since then have suggested that diagnoses using only that original clinical criteria may lead to underdiagnosis. In this review, updated KD diagnostic methods, diagnostic methods for “atypical” KD, diagnostic pitfalls, and other differential diagnoses are discussed. Peripheral blood eosinophil showed important in distinguishing KD from febrile children. We review herein the current literature regarding new biomarkers, scoring systems, and microRNA panels that may aid in the diagnosis of KD, the importance of eosinophil and treatment updates.

Background: allergic diseases and, in particular food allergy (FA), have been identified as one of the major diseases in the world. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility” during which several factors can predispose children to FA development. Changes in gut microbiota composition, from pregnancy to infancy, could have a pivotal role in this regard: some bacterial genus such as Lactobacillus or Bifidobacterium seem to be protective from FA development, on the contrary Clostridium and Staphylococcus appear to be unprotective. Methods: we conducted a research through the most recent literature (2013-2023), using Pubmed and Scopus as databases. We included English original papers, clinical trials, metanalysis and reviews. Case reports, series and letters have been excluded. Results: during pregnancy, maternal diet can play a fundamental role in influencing gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species by human milk oligosaccharides (HMOs), that play a prebiotic role. Also complementary feeding can modify gut microbiota composition. Conclusions: the first two years of life are a critical period where several factors, in genetic predisposed children, can increase the risk of FA development.

This study aimed to present a systematic meta-analysis examining the association between Helicobacter pylori (H. pylori) infection, hemoglobin A1c levels, and the development of type 1 diabetes mellitus. The initial search identified 451 articles related to the association between H. pylori infection and T1DM. Among them, 14 articles had 2,971 participants meeting the inclusion criteria for advanced meta-analysis. A significant association was observed between H. pylori infection and T1DM, with an odds ratio (OR) of 1.87 (95% confidence interval [CI]: 1.27–2.78, p = 0.002). A subgroup analysis on H. pylori status showed that a longer duration of diabetes diagnosis and higher hemoglobin A1c levels were significantly associated with H. pylori infection (p < 0.001 for both). However, there was no significant association between H. pylori infection and the diagnostic age of diabetes (p = 0.306). These findings contribute to the understanding of the association between H. pylori infection and T1DM, thereby highlighting the potential role of H. pylori in influencing the duration and glycemic control of diabetes.

Abstract: Accurately predicting a fetus's gestational age (GA) is of utmost importance in prenatal care. This study aimed to develop an artificial intelligence (AI) model that can automatically predict GA using biometric measurements derived from fetal brain mag-netic resonance imaging (MRI). Additionally, we aimed to assess the significance of con-sidering different references when interpreting GA predictions. To achieve this, we obtained measurements such as Biparietal Diameter (BPD), Fron-to-occipital Diameter (FOD), and Head Circumference (HC) from a dataset comprising 52 normal fetal MRI cases with T2 Haste sequences from Rush University. Both manual and AI-based methods were utilized to acquire these measurements. We also employed three reference papers (Garel, Freq, and Bio) for comparison purposes. The results demonstrated a strong correlation between manual and AI measure-ments, indicating consistency between the two methods. The AI-based measurement of HC exhibited a higher correlation with actual values compared to BPD, FOD, and correct-ed BPD (BPDC). When comparing these measurements with GA in the Picture Archiving and Communication System (PACS), the differences varied depending on the reference used. Specifically, the differences ranged from 0.47 to 2.17 weeks for BPD, 0.46 to 2.26 weeks for FOD, and 0.75 to 1.74 weeks for HC. Furthermore, the Pearson correlation coeffi-cient analysis revealed that all correlation coefficients between PACS records and GA pre-dictions using different references were greater than 0.97. In conclusion, the AI model based on fetal brain MRI accurately predicts GA by uti-lizing BPD, FOD, and HC measurements. The AI approach, which involves combining line segments to calculate fetal head circumference, offers improved accuracy and con-venience compared to manual estimation. This study underscores the potential of AI models in accurately estimating gestational age and highlights their utility in prenatal care. By integrating AI as a valuable tool in prenatal care, we can enhance the accuracy, ef-ficiency, and decision-making involved in assessing fetal development and monitoring pregnancies using MRI measurements.

The influence of diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations of donors’ dietary intake and nutritional status with micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a 5-day weighed dietary record, and collected milk for 5 consecutive days. Nutrient determinations in donors’ erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors’ plasma DHA content and donors’ DHA intake (R2 0.45, p < 0.001). For every 1 g/day of DHA intake, the percentage of DHA in DHM increased by 0.38% (% of total fat) and the percentage of total omega-3 in DHM increased by 0.78% (R2 0.29, p < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, trans fatty acids intake, and breastfeeding duration, and negatively associated with erythrocyte margaroleic acid (R2 0.34, p < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R2 0.57, p < 0.01). Other weaker associations were found for free thiamine, free riboflavin, pyridoxal, dehydroascorbic acid, and lipid profile in DHM. In conclusion, the diet and nutritional status of donors influences the fatty acid profile and micronutrient content of DHM.

Bone marrow mononuclear cells (BMMNCs) have emerged as a potential therapeutic strategy for various incurable conditions including autism spectrum disorder (ASD). To study its safety and efficacy, we analyzed 1011 patients who underwent intrathecal administration of autologous BMMNCs along with neurorehabilitation. At mean follow-up of 19.3 months after intervention, 90.6% patients showed overall improvement. Improvements were observed in attention concentration, command following, eye contact, sitting tolerance, social interaction, hyperactivity, communication, speech, aggressiveness, stereotypical and self-injurious behavior. Statistically significant changes were observed in scores of Indian Scale of Autism Assessment and Childhood Autism Rating Scale (p<0.05). On subgroup analysis, improvements were recorded irrespective of age and disease severity and better outcome was observed in patients who took multiple doses of cell therapy compared to single dose. Comparative Brain PET-CT scan of 401 patients showed improved brain metabolism after the intervention. No major adverse events were reported. Only 9 out of 1011 patients experienced seizures which were managed using medications. 4 out of 9 had history of seizures while 5 had normal EEG with no history. However, improvements were still observed in these 9 patients. Thus, intrathecal transplantation of autologous BMMNCs along with neurorehabilitation is safe and efficacious in patients with ASD.

Background: The role of NFATC genes expression in BAV progression is not fully understood. Aim of study is to determine the significance of NFATC1 and NFATC4 gene expression for myocardial changes in children with BAV. Methods: In 47 children with BAV the standard Doppler echocar-digraphic characteristics were detected and the expression of the NFATC1 and NFATC4 genes was studied. Results: PWTd, AoPPG, in BAV patients were significantly higher compared to healthy controls (PWTd median(min-max) 9 (7-10) mm vs 7 (6-8) mm), AoPPG median (min-max) 7,79 (2,98-15,09) mm Hg vs 2,94 (2,42-3,72) mm Hg. Expression of NFATC1 gene in BAV children was significantly higher compared to NFATC4 (NFATC1 median (min-max) 70,88 (8,79-106,51) e.u. vs 7,72 (1,74-22,67) e.u., respectively p<0,05). Significant correlation of NFATC1 expression with Ao found (R=+0,53, p<0,05). In BAV patients with PWTd > 8 mm and Ao> 21 mm the NFATC1 expression was significantly higher compare to those with PWTd< =8 mm and Ao<=21 mm NFATC1 median (min-max) 45,49 (5,01-101,52) e.u. vs 15,53 (2,36-44,40) e.u., p<0.05 and 81.11 (20.27-101.10) e.u. mm vs 12.16 (2,40-45.49) e.u., p<0.05, respectively) Conclusion: in children with BAV the high expression of the NFATC1 calcineurin signalling pathway gene is associated with elevated PWTd and Ao.

Background: Wilms' tumor (or nephroblastoma) is a malignant and solid neoplasm that derives from the primitive renal bud. It represents the most frequent primary tumor of the urogenital tract in childhood, and treatment consists of surgery and chemo-radiotherapy. However, concerning the quality of life, the new therapeutic frontier is exploring other safer and potentially more effective options, such as minimally invasive surgery and biological drugs. Method: Literature (Pubmed) from January 2013 to March 2023 was reviewed. Results: One hundred five articles were included in the review. Conclusion: In addition to the therapeutic strategies already identified, such as classic surgery and pharmacological therapies, recent studies focus attention on the new frontiers of minimally invasive surgery, such as diagnostics using biomarkers and immunotherapy, which could represent a new therapeutic option and possibly less risky than in the past, contributing in fact to the current knowledge of the scientific panorama in terms of "tumor microenvironment" and systemic implications deriving from oncological disease.

Autism spectrum disorders (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by food selectivity in a significant portion of the population. The nature of this selectivity remains unclear, with hypotheses suggesting associations with sensory disorders or stereotypical and repetitive patterns of activity and interests. This study aimed to determine the prevalence and nature of food selectivity traits in individuals with ASD compared to the neurotypical population. The study involved 219 participants, with 115 diagnosed with autism and 92 without. 12 children undergoing diagnosis were excluded from the analyses. Findings revealed that food selectivity traits are more common in individuals with ASD, with differences in preferences mainly involving structure, color, taste, and serving method. Children with ASD had more food selectivity traits than those without, and certain food characteristics could alter intake as they grow. Selectivity occurred for both sensory and stereotypical reasons, but stereotypical features significantly differentiated neurotypical individuals from those with ASD.

Streptococcus pneumoniae is one of the associated bacteria that can cause the rare but high mortality hematological disease known as purpura fulminans (PF) in both adults and children. Patients with PF can progress quickly to sepsis and multiorgan failure, especially in immunocompromised individuals and young children. Due to the thrombotic blockage of blood arteries in PF, there is diffuse intravascular thrombosis and hemorrhagic infarction of the skin, which evolves from ecchymosis to skin necrosis, risk of limb sequelae, sepsis and fatality. We present a case of a previously healthy 1-year and 9-month female who was admitted to the Intensive Care Unit of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș"- Bucharest, Romania. The patient presented with erythematous patches on left upper limb and trunk, tachycardia, tachypnea, hypotension, anuria and altered sensorium with an indication of intubation for 8 Glasgow Coma Scale (GCS). Cerebrospinal culture grew Streptococcus pneumoniae serotype 1. She required peritoneal dialysis due to acute kidney injury (AKI) and surgeries for affected areas. After multiple organ system failures, our patient evolved rapidly to irreversible tissue necrosis and death. We aim to report a rare case of PF associated with pneumococcal meningoencephalitis in immunocompetent children to better appreciate the risk of fatal evolution when managing this disease in children. To date, few studies report favourable evolution. We discuss the etiology, rapid diagnosis and treatment of immunocompetent children with PF and the importance of interprofessional teams to increase the outcomes in patients with infectious diseases.

Embryo and fetus grow in a hypoxic environment. Intrauterine oxygen levels fluctuate throughout the pregnancy allowing the oxygen to modulate apparently contradictory functions, such as the expansion of stemness but also differentiation. We have recently demonstrated that in the last weeks of pregnancy oxygenation progressively increases, but the trend of oxygen levels during the previous weeks remains to be clarified. In the present study, umbilical venous and arterial oxygen levels, fetal oxygen extraction, oxygen content, CO2, and lactate were evaluated in a cohort of healthy newborns with gestational age &lt; 37 weeks. A progressive decrease in pO2 levels associated with a concomitant increase in pCO2 and reduction of pH has been observed starting from the 23rd week until approximately the 33-34th week of gestation. Over this period, despite the increased hypoxemia, oxygen content remains stable thanks to increasing hemoglobin concentration, which allows the fetus to becoming more hypoxemic, but not more hypoxic. Starting from the 33-34th week, fetal oxygenation increases and ideally continues following the trend recently described in term fetuses. The present study confirms that oxygenation during intrauterine life continues to vary even after placenta development, showing a clear biphasic trend. Fetuses, in fact, from mid-gestation to near-term become progressively more hypoxemic. However, starting from the 33-34th week, oxygenation progressively increases until birth. In this regard, our data suggest that the placenta is the hub that ensures this variable oxygen availability to the fetus, and we speculate that this biphasic trend is functional to the promotion, in specific tissues and at specific timing, of stemness and intrauterine differentiation.

Originating in the 1970s, Magnetic Compression Anastomosis (MCA) has lately been revisited with a focus on minimal invasive surgery (MIS). The aim of this report is to reappraise our earlier experience with MCA with the intention of facilitating future MCA advancement. A retrospective review was conducted regarding preclinical experiments and clinical trials at a single institution from 1980 through 1995. The reviewed information was compiled and appraised to generate proposals for future MCA use. The experimental studies, including 250 MCA cases in gastrointestinal and urinary tract animal models, demonstrated the technical versatility of MCA as well as the superior biomechanical characteristics in comparison to hand-sewn anastomoses. Clinical trials encompassed 87 MCA procedures in 86 children, 2 to 10 years of age, involving the following techniques: non-operative esophageal recanalization (n=15), non-operative ileostomy undiversion (n=46), Swenson pull-through (n=10), non-operative urethral recanalization (n=5), and extravesical ureterocystoneostomy (n=11). Clinical MCA was found to be successful in over 87% of cases. MCA limitations concerning anastomotic failure and scarring were thought to be mostly due to inadequate magnetic compression. Based on our historic experience, we propose further research on the technical aspects of MCA, along with the biologic aspects of anastomotic tissue remodeling. Magnets should be designed and manufactured for a wide spectrum of pediatric surgical indications, particularly in combination with novel MIS techniques.

Bibliometric studies on inherited metabolic diseases(IMDs) didn't exist in the literature.Our research aims to conduct a bibliometric study to determine the current status,trending topics,and missing points of publications on IMDs.Between 1968-2023, we conducted a literature search with keyword "inherited metabolic disease" in the SCOPUS-database.We included research articles in medicine written in English,published in the final section.We created our data pool using VoSviewer, SciMAT, and Rstudio software programs for bibliometric parameters of the articles that met the inclusion criteria.We performed bibliometric analysis of the data with R-package "bibliometrix" and BibExcel programs.We included 2702 research articles published on IMDs.Top three countries that have written the most articles in this field are; USA(n= 501), United Kingdom(n=182), and China(n= 172).The most preferred keywords by the authors were;newborn screening(n=54), mutation(n=43), phenylketonuria(n=42), children(n=35), genetics(n= 34) and maple syrup urine disease(n=32).Trending topics were osteoporosis, computed tomography, bone marrow transplantation in the early years of the study, chronic kidney disease, urea cycle disorders, next-generation sequencing, newborn screening, and familial hypercholesterolemia in the final years of the study. This study provides clinicians with a new perspective showing that molecular and genetic studies in inherited metabolic diseases will play an essential role in diagnosis and treatment in the future.

Ascites is a term that describes a pathological accumulation of fluid in a peritoneal cavity. It is generally a rare occurrence in a pediatric population and is most commonly associated with liver failure and cirrhosis. In that case, a diuretic treatment is usually implemented to relieve the ascites as it forms in the mechanism of water retention and water leakage from the portal venous system due to portal hypertension. It is important to note however that many other issues may cause ascites in children. Those require a catered approach suited to the pathomechanism of ascites formation in those underlying conditions. That is why a complex diagnostic process ought to be run in pediatric patients with ascites to correctly identify a condition causing it and provide the patient with adequate and thorough care.

Sex/gender (S/G) differences in ASD language profiles have been poorly investigated. The present study aims to explore whether male (M) and female (F) children with ASD and with normal non-verbal cognitive abilities differ in their linguistic profiles. A sample of 76 Italian children with ASD (range: 4.9 – 8 years), including 50 M and 26 F, was retrospectively recruited. Language profiles were analyzed using standardized tests for the evaluation of receptive and expressive vocabulary as well as grammar. Grammatical comprehension was the most impaired domain compared to the other language measures in both M and F children. Comparing language profiles between S/G, F showed significantly better scores than M in grammatical production (p=.002), and M showed better active negative sentences comprehension (p=.035). Moreover, comparing the language profiles between M and F with receptive disorder, F had significantly worse grammatical comprehension and better grammatical production than M. Even among children without receptive disorder, F had significantly higher grammatical production scores. The S/G differences in language profile, particularly better expressive language in F than M, can partially contribute to the delayed ASD diagnosis or underdiagnosis of F without intellectual disability. Finally, our results document the importance of accurately investigating both expressive and receptive abilities in children with ASD.

Family Integrated Care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of FICare in critically ill infants in the first few weeks of life. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in observational group receiving standard care (SC)and 24 in the FICare Plus group. Resources were developed for staff and parents to support earlier engagement in infant care. Outcomes were assessed using standardized questionnaires. The t-test or Wilcoxon Rank-Sum test were used to compare continuous variables, while Chi-square or Fisher exact test were used for categorical variables, respectively. Baseline maternal and infant characteristics were similar in both groups. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infant with no increase in adverse events and no increase in parent stress. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrolment {83.1 (67-94) vs 77.3 (66-86); p-value 0.4}. However, the scores prior to discharge were lower in FICare Plus group {78 (71-90) vs 63 (52-74.5); p-value 0.02}. This pilot study showed that it is feasible and safe to implement family integrated care in critically ill infants.

The purpose of this study was to quantify characteristics of bimanual movement intensity during 30-hour Hand Arm Bimanual Intensive Therapy (HABIT) and bimanual performance (activities and participation) in real-world using accelerometers in children with unilateral cerebral palsy (UCP). Twenty-five children with UCP participated in a 30-hour HABIT program. Data was collected from bilateral wrist-worn accelerometers during 30-hours HABIT to quantify the movement intensity, and three days pre- and post-HABIT to assess real-world performance gains. Movement intensity and performance gains were measured using six standard accelerometer-derived variables. Bimanual capacity (body function and activities) was assessed using standardized hand function tests. We found that accelerometer variables increased significantly during HABIT, indicating increased bimanual symmetry and intensity. Post-HABIT, children demonstrated significant improvements in all accelerometer metrics, reflecting real-world performance gains. Children also achieved significant and clinically relevant changes in the hand capacity following HABIT. Therefore, our findings suggest that accelerometers can objectively quantify bimanual movement intensity during HABIT. Moreover, HABIT enhances hand function as well as activities and participation in real-world situation in children with UCP.

BACKGROUND: It has been known for decades that breastfeeding leads to a lower risk of asthma, respiratory infections, or metabolic syndrome at school age. In addition, evidence is now accumulating on the influence of breast milk on the shape, volume, or function of the heart and lungs. Within this field of research into the effects of breast milk on the structure of the heart and lungs, we have set out to analyze the differential electrocardiographic characteristics of schoolchildren who were once breastfed. METHOD: Observational cross-sectional study including 138 children aged 6 or 12 consecutively presenting to a well-child clinic between May and December 2022. Inclusion criteria: the ability to perform reproducible ECG records, the feasibility of weighing and measuring patient, and breastfeeding data collected from birth. RESULTS: Using the 40º cut-off value for the mean P-wave axis among schoolchildren, 76% of never breastfed children in our sample have a P-wave axis in a more vertical position than the mean as compared to 58% of ever-breastfed children (OR:2.25;95%CI:3.13-1.36); there was no other significant difference between infant feeding groups in somatometric characteristics or ECG parameters, CONCLUSION: We found a significant difference of the mean values of the P-wave axis between never and ever breastfed children. Although this report should be approached cautiously, these findings add to the renewed interest in discerning developmental interventions to improve cardiovascular health.

A high prevalence of childhood obesity has been observed in the last years. Ultrasound of adi-pose tissue is technique validated in adults in order to detect risk of comorbidity as NAFLD and NASH, but no studies at pediatric population. The main objective is to assess measurement of preperitoneal fat by nutritional ultrasound as a screening method for non-alcoholic fatty liver disease (NAFLD) in obese children. Patients and methods: Prospective longitudinal study. A study of somatometry, bioelectrical impedancemetry and nutritional ultrasound has been car-ried out. Results : 102 patients were included, with a mean BMI (SDS) of 2.58. A linear and direct correlation was observed between the fat mass measured by bioelectrical impedancemetry and the total subcutaneous abdominal fat measured by nutritional ultrasound. We also observed a correlation between preperitoneal fat measured by nutritional ultrasound and NASH, with a cut-off point of 0.93 cm of preperitoneal fat (sensitivity 96% and specificity 94%).Conclusions: Measurement of preperitoneal fat by nutritional ultrasound is a good screening method for NASH in obese children.

Congenital cytomegalovirus (cCMV) infection resulting from non-primary maternal infection or reactivation during pregnancy can cause serious fetal-neonatal sequelae. We describe a male newborn born at term, with signs of perinatal asphyxia, and intractable acute provoked seizures, in the context of severe cCMV infection. The newborn was delivered in a referral hospital by emergency caesarean section due to fetal distress. Due to signs of asphyxia at birth and clinical moderate encephalopathy (Sarnat 2), he was transferred to our center for therapeutic hypothermia. Continuous full video-electroencephalography monitoring showed no seizures during the first 72 hours, however, soon after rewarming, he presented refractory status epilepticus. Cranial ultrasonography revealed bilateral ventricular and intraparenchymal hemorrhage. Routine infectious screen-ing on urine, blood, cerebrospinal fluid, and nasopharyngeal secretions revealed positive CMV DNA Polymer-ase Chain Reaction (PCR) on all samples. The CMV DNA performed on the bloodspot (Guthrie) card taken at birth yielded a positive result, confirming the intrauterine transmission and congenital origin of the infection. Maternal non-primary CMV infection in pregnancy is transmitted to the fetus in 0.5-2% of cases. When transmitted, it may cause serious fetal abnormalities, complications in the immediate neonatal period, and se-vere sequelae later in childhood. During pregnancy, it is useful to monitor maternal serology for CMV, even in previously immunized mothers, to identify signs of new infection or viral reactivation and implement measures to prevent neonatal sequelae. The possible advantages of standardized CMV screening of all newborns are a pertinent discussion point, as this may enable us to identify affected neonates timeously and prevent long term disabilities.

Neonatal apnoea has been treated with caffeine, affecting the central nervous and the cardiovascular system. Heart rate variability (HRV) reflects the activity of the autonomic nervous system (ANS) and might be used as a measure of ANS maturation in newborns. We aimed to establish the effect of caffeine on HRV in newborns and sought for a potential correlation between HRV and the postmenstrual age. In 25 newborns hospitalized due to apnoea and treated with caffeine (2.5 mg/kg), we assessed breathing frequency, arterial oxygen saturation, body temperature, and the heart rate, while they were sleeping. We assessed HRV by spectral analysis using fast Fourier transformation. The same protocol was reapplied 100 hours after caffeine withdrawal to assess control parameters. Caffeine increased breathing frequency (p=0.023) but did not affect any other parameter assessed including HRV. We established a positive correlation between postmenstrual age and HRV during treatment with caffeine as well as after caffeine had been withdrawn (total power: p=0.044; low-frequency band: p=0.039). Apparently, the maintenance dose of caffeine is too low to affect the heart rate and the HRV. A positive correlation between postmenstrual age and HRV might reflect maturation of ANS, irrespective of caffeine treatment.

Introduction The increase in survival of extremely preterm infants has led to increased rates of bronchopulmonary dysplasia (BPD). Therefore, a potential role of human milk feeding in protecting against this condition has been suggested. Material and methods Retrospective descriptive study based on data about morbidity in the population of infants born from 22+0 to 26+6 weeks of gestation, included in the Spanish network SEN1500 during the period 2004-2019 and who were alive at discharge. The primary outcome was moderate-severe BPD. In addition, associated conditions were studied, including breastfeeding at discharge. The temporal trends of BPD and breastfeeding rates at discharge were also studied. Results In the study population of 4341 infants who survived to discharge, the rate of moderate-severe BPD was 43,7% and increased over the period to a rate >50% in the last three years. The factors significantly associated with a higher risk of moderate-severe BPD were male sex, high-frequency oscillatory ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis. Exclusive human milk feeding at discharge and any amount of human milk at discharge were associated with a lower incidence of moderate-severe BPD (OR 0.752, 95% CI 0.629-0.901, and OR 0.714, 95% CI 0.602-0.847, respectively). The rates of human milk at discharge in infants with moderate-severe BPD increased over the period. In the last years, more than one-third of extremely preterm infants were discharged on exclusive human milk feeds, and about two-thirds of them on any amount of human milk feeding. Conclusions
The results of the present study strongly support the role of any amount of human milk in preventing BDP in extremely preterm infants.

Functional somatic disorders (FSD) characterized by persistent and disabling physical symptoms are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study evaluates the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) included in a randomized trial testing group-based therapy (AHEAD) received systematic assessment (4 hrs.) and a subsequent psychiatric consultation (1.5 hrs.). Clinical outcomes included self-reported physical health, symptom severity, illness perception, illness related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen on symptom severity, illness worry, negative illness perceptions, limiting illness behavior and psychological inflexibility. The results underpin the importance of systematic assessment and psychoeducation which may be effective in their own right in specialized treatment of adolescents with severe FSD.

Appropriate nutrition during pregnancy and the post-partum period is vital to both the parent and their offspring. Both under- and over-nourished status may have important microbial implications on the parental and infant gut microbiomes. Alterations to the microbiome can have implications for a person’s risk of obesity and metabolic diseases. In this review, we examine alterations in the parental gut, vaginal, placental, and milk microbiomes in the context of pre-pregnancy BMI, gestational weight gain, body composition, gestational diabetes, and parental diet. We also investigate how the infant gut microbiome may be altered by these different parameters. Many of the microbial changes seen in under- and over-nourished states in birthing parents may result in long-term implications to the health of offspring. Differences in diet appear to be a major driver of the parental, and subsequently milk and offspring microbiomes. Further prospective longitudinal cohort studies are needed examining nutrition and the microbiome to better understand its implications. Additionally, trials involving dietary interventions in child-bearing age adults should be explored to improve the parent and child’s risks for metabolic diseases.

Background: Children with anorectal malformation (ARM) require long-term follow-up, especially for fecal continence and main predictors of longer-term success are the type of ARM, associated anomalies and sacral integrity. Three-Dimensional High Resolution Anorectal Manometry (3D-HRAM) provides an image of the pressure profile of anal sphincter complex. Aim of study was to evaluate the anal sphincter function in ARM patients with 3D HRAM correlating this analysis to clinical outcome and to associated malformations. Methods: Forty ARM patients, were submitted to 3D HRAM: manometric, anatomical and clinical score were correlated to response to bowel management (BM). Results: A positive correlation between all scores and type of ARM was found: in high ARM and in patients with spinal anomalies (regardless to ARM type) lower scores were reported and even after BM they do not achieve good continence. Conclusions: 3D-HRAM provides information on the functional anatomy of the sphincter complex. Our study shows good correlation between the manometric results and clinical outcome, confirming spinal malformations and ARM type as most important prognostic risk factors for poor outcome. Specific sphincteric defects can be explored with manometry, allowing for tailored bowel management strategies.

Preterm delivery can be precipitated by infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. 90 infants had suspected prenatal infection and 63 were diagnosed with postnatal infection. Independent of gestational age at delivery, MCP-1 was significantly increased (P &lt; 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (P&lt;0.01) and CRP was increased (P&lt;0.05) in the presence of chorioamnionitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age. In those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants born exclusively for maternal indications.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "Classic" BPD, as per the original description, is less common now. "New BPD," which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving due to medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of vulnerable neonatal population given the dearth of safe and effective therapeutic options. Evidence from studies mainly in adults is now available for several novel antimicrobial compounds, such as new β-lactam/β-lactamase inhibitors (e.g. ceftazidime-avibactam, meropenem-vaborbactam, imipenem/cilastatin-relebactam), although old antibiotics such as colistin, tigecyclin and fosfomycin are also encombassed in the fight against MDR-GN infections that remain challenging. Data in the neonatal population are scarse, with few clinical trials enrolling neonates for the evaluation of efficacy, safety and dosing of new antibiotics, while the majority of old antibiotics are used off-label. In this article we review data about some novel and old antibiotics that are active against MDR-GN bacteria causing sepsis and are of interest to be used in the neonatal population.

Prediction of survival in very preterm infants is very important in terms of clinical medicine and parent counseling. In this prospective study involving 96 very preterm infants, we evaluated whether metabolomic analysis of gastric fluid and urine samples obtained soon after birth could predict survival on days of life (DOL) 3 and 15 as well as overall survival up to hospital discharge. Gas chromatography-mass spectrometry (GC-MS) profiling was used. Uni- and multivariate statistical analyses were carried out to evaluate significant metabolites and their prognostic value. Differences in several metabolites were identified between survivors and non-survivors at the time-points of the study. Binary logistic regression showed that certain metabolites in the gastric fluid including arabitol as well as succinic, erythronic and threonic acids was associated with DOL 15 and overall survival. Gastric glyceric acid was also associated with DOL 15 survival. Urine glyceric acid could predict survival on DOL 3 and overall survival. In conclusion, non-surviving preterm infants showed a different metabolic profile compared survivors showing a significant discrimination with the use of GC-MS-based gastric fluid and urine analysis. Results of this study support the usefulness of metabolomics in developing survival biomarkers in very preterm infants.

Mothers’ own milk (MOM) for premature babies is considered a life-saving drug for its proven protective action against the complications of prematurity and for the effects on the outcome in the short and long term, especially the neurological one. We studied the use of the MOM for WLBWs over a 5-year period. Statistical comparisons concerned data on feeding with the MOM during stay in NICU and at discharge with respect to maternal and neonatal variables (gestational age, birth weight, type of pregnancy if single or twin, maternal age) and to feeding data (timing of the start of the Minimal Enteral Feeding and the availability of the MOM, the achievement of the Full Enteral Feeding, the type of nutrition at discharge). We observed an increase, between 2017 and 2021, of MOM use (p=0.003). The availability of the MOM occurred on average on the fourth day of life and improved over the years. Start of MEF with human milk averaged 1.78 days and 54.3% of VLBWs received MEF with donor milk on the first day of life (50% within the first 6 hours). The average MOM at discharge was 47.6% with 36.1% exclusive MOM (EMOM) and an increase from 45.8% in 2017 (EMOM 33.3%) to 58.82% (EMOM 41.18%) in 2021. The mean average daily growth of the weight improved (p<0.001) during this period. There is no statistical difference between infants fed with MOM and those fed with bank milk. The maternal age, the start day of the MOM feeding and gestational age have a significant impact on the type of feeding at discharge.

(1) Birth asphyxia is the major cause for delivery room resuscitation. Subsequent organ failure and hypoxic-ischemic encephalopathy (HIE) account for 25% of all early postnatal deaths. The neonatal Sequential Organ Failure Assessment (nSOFA) considers platelet count, respiratory and cardiovascular dysfunction in neonates with sepsis. To evaluate whether nSOFA is also a useful predictor for in-hospital mortality in neonates (≥ 36+0 weeks of gestation (GA)) following asphyxia with HIE and therapeutic hypothermia (TH), (2) nSOFA was documented at ≤ 6 hours of life. (3) 65 infants fulfilled inclusion criteria for TH. All but one infant received cardiopulmonary resuscitation and/or respiratory support at birth. nSOFA was lower in survivors (median 0 [IQR 0-2]; n = 56, median GA 39+3, female n = 28 (50%)) than in non-survivors (median 10 [4-12], p < 0.001; n = 9, median GA 38+6, n = 4 (44.4%)). This was also observed for the respiratory (p < 0.001), cardiovascular (p < 0.001), and hematologic sub scores (p = 0.003). The odds ratio for mortality was 1.6 [95% CI = 1.2 – 2.1] per one-point increase in nSOFA. The optimal cut-off value of nSOFA to predict mortality was 3.5 (sensitivity 100.0%, specificity 83.9%). (4) Since early accurate prognosis following asphyxia with HIE and TH is essential to guide end-of-life decisions, nSOFA (≤ 6 hours of life) offers the potential to identify infants at risk of mortality.

Background: Primary infection has been questioned as the pathogenetic cause of acute appendicitis. We attempted to identify the bacteria involved, and to investigate if their species, types, or combinations affected the severity of acute appendicitis in children. Methods: Samples from both the appendiceal lumen and the peritoneal cavity of 72 children who underwent appendectomy were collected to perform bacterial culture analysis. The outcomes were studied to see if and how they were associated with the severity of the disease. Regression analysis was performed to identify any risk factors associated with complicated appendicitis. Results: Escherichia coli, Pseudomonas aeruginosa and Streptococcus species were the most common pathogens found in the study population. The same microorganisms, either combined or separate, were the most common in the appendiceal lumen and the peritoneal cavity of patients with complicated appendicitis. Gram-negative bacteria, polymicrobial cultures in the peritoneal fluid and in the appendiceal lumen, were associated with complicated appendicitis. Polymicrobial cultures in the peritoneal cavity presented four times higher risk of complicated appendicitis. Conclusion: Polymicrobial presentation and gram-negative bacteria are associated with complicated appendicitis. Antibiotic regimens should target the combinations of the most frequently identified pathogens, speculating the value of early antipseudomonal intervention.

The 22q11.2 deletion syndrome is a multisystemic disorder characterized by a marked variability of phenotypic features making the diagnosis challenging for clinicians. The wide spectrum of clinical manifestations includes congenital heart defects, most frequently conotruncal cardiac anomalies, thymic hypoplasia and predominating cellular immune deficiency, laryngeal developmental defects, midline anomalies with cleft palate and velar insufficiency, structural airway defects, facial dysmorphism, parathyroid and thyroid gland hormonal dysfunctions, speech delay, developmental delay, neurocognitive and psychiatric disorders. Significant progress has been made in understanding the complex molecular genetic etiology of the 22q11.2 deletion syndrome underpinning the heterogeneity of clinical manifestations. The deletion is caused by chromosomal rearrangements in meiosis and is mediated by non-allelic homologous recombination events between low copy repeats or segmental duplications in the 22q11.2 region. A range of genetic modifiers, environmental factors as well as the impact of hemizygosity on the remaining allele contribute to the intricate genotype-phenotype relationships. This comprehensive review has been aimed at highlighting the molecular genetic background of 22q11.2 deletion syndrome in correlation with a clinical multidisciplinary approach.

Kawasaki disease is a form of acute febrile multisystem vasculitis. In Japan, the Kobayashi score is used to predict intravenous immunoglobulin resistance and subsequent complications, including coronary artery abnormalities, in children with Kawasaki disease. If the score is high, it is standard practice to use steroids in the initial treatment of the disease. In this study, we describe a pediatric case of coronary artery abnormality formation after acute steroid treatment for Kawasaki disease, despite the lack of an inflammatory response and Kawasaki disease symptoms. The use of steroids with acute Kawasaki disease patients can mask laboratory findings and clinical symptoms. Echocardiogram should be considered an equivalent technique to physical examination.

Background: In healthy children, the frequency of anomalous persistence of primitive reflexes (PRs) and craniosacral blocks (CBs) are unknown, as well as their impact on neurodevelopment, behaviour disorders and related consequences. We aim to know the prevalence of anomalous PRs and CBs in apparently healthy children and its relationships with behavior and neurodevelopment anomalies. Methods: Participants (n=120) were evaluated through physical examination to detect PRs and CBs, an ad hoc parent survey to collect perinatal events, and children behavior assessment by teachers using Battelle score. Results: PRs were present in 89.5%. Moro (70.8%), cervical asymmetric (78.3%) and cervical symmetric PRs (67.5%) were the most frequent observed PRs. CBs were found in 83.2%, and the most frequent CBs were dura mater (77.5%) and sphenoid bone (70%) blocks. Moro, cervical asymmetric and cervical symmetric active primitive reflexes are significantly associated to cranial blocks of dura mater, parietal zones, and sphenoid bone sway. Gestational disorders or perinatal complications were associated to a higher frequency of PRs and CBs. The presence of PRs and CBs were associated with abnormal Battelle scores and neurobehavioral problems. Conclusion: Presence of PRs and CBs in children without diagnosed diseases are frequent and related with disturbances in childhood neurodevelopment.

Since 2000, caffeine is used as citrate salt of caffeine for treatment of apnea of prematurity. However, it remained elusive if caffeine citrate has a direct function in the respiratory epithelium, potentially as modulator for ciliary beat frequency (CBF) regulation in human respiratory cells (hRECs). Here, we studied the mechanism of action of caffeine citrate on the respiratory epithelium on hRECs derived from healthy donors and individuals with cystic fibrosis (CF) cultured under air-liquid-interface (ALI) conditions. CBF analyses of hRECs were performed by high-speed video microscopy. In the presence of caffeine, hRECs show a significant increase in CBF over ciliary base frequency (CBFb), demonstrating a direct influence of caffeine on ciliary function. We also demonstrate a specific action of caffeine at ryanodine receptor (RYR) channels, mediating calcium efflux from intracellular stores to increase CBF. We describe a novel pharmacological effect of caffeine citrate - direct increase of CBF of primary hRECs cultured at ALI. Caffeine citrate has certain advantages over other methylxanthines: it was shown to have stable plasma concentration, longer half-life, and is better tolerated than e.g. theophylline. We conclude that caffeine citrate therapy might be suitable strategy to treat respiratory diseases with compromised mucociliary clearance.

Neonatal drug information (DI) is essential for safe and effective pharmacotherapy in (pre)term neonates. Such information is usually absent from drug labels, making formularies a crucial part of the neonatal clinician’s toolbox. Several formularies exist worldwide, but they have never been fully mapped nor compared for content, structure and workflow. The objective of this review was to identify neonatal formularies, explore (dis)similarities, and raise awareness of their existence.Neonatal formularies were identified through self-acquaintance, experts and structured search. A questionnaire was sent to all identified formularies to provide details on formulary function. An original extraction tool was employed to collect DI from the formularies on the 10 most commonly used drugs in pre(term) neonates.Eight different neonatal formularies were identified worldwide (Europe, USA, Australia-New Zealand, Middle East). Six responded to the questionnaire and were compared for structure and content. Each formulary has its own workflow, monograph template and style, and update routine. Focus on certain aspects of DI also varies, as well as the type of initiative and funding.Clinicians should be aware of the various formularies available and their differences in characteristics and content to use them properly for the benefit of their patients.

Psychomotor developmental delay in infants includes failure to acquire abilities such as sitting, walking, grasping objects and communication at the ages when most infants have acquired these abilities. Known risk factors include a large number of aspects of family environment, socioeconomic position, problems in pregnancy and birth, and maternal health. It is clinically useful to be able to screen for developmental delay so that healthcare interventions can be considered. The present research used machine learning (random forest) to create an algorithm predicting psychomotor delay in 9-month-old infants using information ascertainable at birth and in early infancy. The dataset was the UK longitudinal Millennium Cohort study. Fifty-two predictors measuring socioeconomic indicators, paternal, family and social support for the mother, beliefs about good parenting, maternal health, pregnancy and birth were included in the initial algorithm. Feature reduction showed that of the 52 variables, birthweight, family income and parents’ ages had the highest feature importance scores and could alone correctly predict developmental delay with over 99% sensitivity and 100% specificity. The relationships between delay and some of the predictors, particularly income, were nonlinear and complex. The results suggest that the risk of psychomotor developmental delay can be identified in early infancy using machine learning, and that the best predictors are factors present prior to birth. Surprisingly, the most important factors included in the present study did not include illnesses during pregnancy such as eclampsia and infections.

Objective: This study aimed to determine impact of eHealth literacy on health promotion activities and preventive health practice among adolescents. Methods: This cross-sectional study was conducted between March and May 2022 with 706 adolescents in Çorum, Turkey. A face to face questionnaire form including socio demographic characteristics, preventive health practices, eHealth Literacy scale and Adolescent Health Promotion Scale were used. The data of the research were analyzed with the SPSS 22.0 program. Percentage, mean, Pearson Correlation analysis and multiple regression analysis were used in the analyzes. The p<0.05 value was considered statistically significant in the evaluations. Results: In the study, 55.8% were female and the mean age of the whole group was 16.09±2.63 years. The mean score of eHealth Literacy scale was 29.40±6.29. The mean of the total scores obtained from the Adolescent Health Promotion Scale was 137.97±21.87. Among the adolescents 96.0% didn’t use alcohol and 81% didn’t smoke. The rate of annual weight measure was 68.8%. Measurements of annual blood pressure, annual blood iron, annual cholesterol, annual dental examination and regular exercise rate were below 50%. There was a significant positive correlation between eHealth literacy and the Adolescent Health Promotion Scale (p<0.001). Multiple linear regression analysis was performed to predict eHealth literacy using the variables of Adolescent Health Promotion and preventive health practices. eHealth literacy was positively and significantly predicts health promotion behaviors (β= 0.27, t (695)= 7.54, p<0.001). eHealth literacy increased annual weight measurement by more than 0.13 (β=0.13), the annual blood iron measurement by more than 0.16 (β=0.16), annual dental examination by more than 0.11 (β=0.11). Conclusions: Adolescents ehealth literacy was high and effected via health promotion activities and preventive health practices. Developing eHealth litracy interventions will be important for environments with a high concentration of adolescents (schools, courses). Also, primary health care services should be entegrated with school environment.

Background & Objective. Perinatal hypoxia acutely triggers the release of cytokines and chemokines from neurons, astrocytes and microglia. In response to hypoxia-ischemia resting/ramified microglia proliferate and undergo activation, with the production of proinflammatory molecules. The brain damage extension seems to be related with both the severity of hypoxia and the balance between pro and anti-inflammatory host response. Methods: In this preliminary study we compared in 10 neonates with hypoxic ischemic encephalopathy (HIE), during therapeutic hypothermia (TH), plasmatic cytokines and other inflammatory molecules levels: monocytic chemotactic-protein-1 (CCL2/MCP-1), CXCL8, glial fibrillary acidic protein (GFAP), Interferon gamma (IFN y), Interleukin 10 (IL-10), IL-18, IL-6, CCL3, ENOLASE2, Colony Stimulating Factor(GM-CSF), IL-1b, IL-12p70, IL-33, Tumor Necrosis Factor alpha(TNF), collected at four different time points during TH (24 hours, 25-48 hours, 49-72 hours) , and after the rewarming (7-10 days from birth). Five of enrolled babies had pathological brain MRI (“cases”) and 5 had a normal examination (“controls”). Cytokines were measured by Magnetic Luminex Assay (Luminex SV 013-17 (14), instrument Biorad Bio-Plex 100 s.n. LX 10005039304). MRI images were classified according to the Barkovich score. Results: Mean levels of all cytokines and molecules at time T1 were not significantly different in the two groups of patients. Comparing samples paired by day of collection, the greatest differences between cases and controls were found at times T2 and T3, during TH. After rewarming, some molecules showed an upward trend. At T4, levels tended to be close again (with the exception of IL-6, IL10 and IL18). Infants with worse MRI showed plasmatic GFAP levels higher than those with normal MRI, while their IL-18 was lower. Mean levels of CCL3MIP1alpha, GMCSF, IL1BETA overlapped throughout the observation period in both the groups of neonates. Conclusion. In children with worse brain MRI we found high levels of GFAP and of IL-10 at T4, considered respectively an early biomarker of brain damage and a predictor of adverse outcome, according to the literature, and a trend towards low IL-18 levels. We found the greatest, although not significant, difference between molecules levels in cases and controls at time points T2 and T3, during TH. With the rewarming some molecules showed an upward trend. We cannot exclude that the small sample size may prevent significance in the differences from being achieved.

Abstract: Introduction: Covid-19 lockdown has caused important changes in children's routines, especially in terms of nutrition, physical activity, screen time, social activity, and school time. Regarding these changes, recent studies show that Covid-19 lockdown was associated with higher levels of anxiety and depression in children. The objective of this study was to assess changes in sleep quality in Spanish children during lockdown decreed by the Spanish government between March and June 2020. Methodology: We compared the BEAR score of 478 participants in the SENDO project at the periods before, during and after lockdown. We used hierarchical models with two levels of clustering to account for the intra-cluster correlation between siblings. Interaction of time with and a set of a priori selected variables was assessed by introducing the interaction term into the model and calculating the likelihood ratio test. Results: Mean scores in the BEAR questionnaire referred to the periods before, during, and after lockdown were 0.52 (sd 1.25), 1.43 (sd 1.99) and 1.07 (sd 1.55), respectively, showing a worsening of sleep quality as a result of confinement. Parental level of education was found to be an effect modifier (p for interaction=0.004). Children whose parents had higher education (university graduates or higher) showed a smaller worsening than those without. Conclusion: We found that the mean score in the BEAR questionnaire significantly worsened during lockdown and significantly improved after it. However, it did not reach the initial level. The mean score in the BEAR questionnaire referred to the period after lockdown was significantly higher than before.

Children under two years old are at risk for anemia because young children have an increased need for iron for their physical growth and brain development. The purpose of this study was designed to evaluate the effects of a caregiver potential support program on anemia prevention in children six months to two years old attending the subdistrict health-promoting hospital in Thasala District, Nakhon Si Thammarat Province. This study was quasi-experimental. The sample included children aged six months to two years old and their caregivers, who were selected by random sampling and allocated to either the experimental or control group, with 40 pairs per group. The experimental group received a potential support program, while the control group received regular care. Both groups were followed for 12 weeks. The instruments used were the potential caregiver assessment, children’s anemia assessment, and a program to support the potential of primary caregivers. Descriptive statistics, chi-square, and t-tests were used to analyze the data. The results revealed that 11.4% of the children had anemia, and a hematocrit count of less than 33% (range = 30-40, M = 34.89, SD = 1.97). The mean scores of knowledge about anemia and iron supplementation after using the program in the experimental group and control group were significantly different (p < 0.001). The mean scores of knowledge about anemia in the experimental and control group were 15.75, SD = 0.54, and 13.28, SD = 1.43 respectively. The mean scores of knowledge about iron supplementation in the experimental and control group were 10.75, SD = 0.49, and 8.15, SD = 1.54 respectively. It was found that the experimental group had a higher mean score on food care behaviors than the control group for 6-11 months and 1-2 years, with statistical significance. The experimental group also had a higher mean score of care behaviors concerning children’s consumption of medicine than the control group (M = 58.20, SD = 4.05; M = 45.78, SD = 9.66, respectively), (p < 0.001). The mean score of the hematocrit level for the experimental group was found to be higher than the control group after receiving the program (M = 35.80, SD = 1.55; M = 34.83, SD = 2.14, respectively), (p < 0.05). Therefore, healthcare providers should support caregivers' capacity to provide continued care for children to prevent anemia.

Today, various questionnaires are available to assess Adverse Childhood Experiences (ACEs) in children; however, it is uncertain if these questionnaires comprehensively address the adversities of vulnerable subgroups, specifically refugee children. This review's objectives are to (1) identify current ACE questionnaires and determine if they are suitable for assessing refugee children’s adversities, and (2) identify those previously used within a refugee population. A systematic literature search was conducted across five databases for articles published since 2010, including studies using an ACE questionnaire that recognized multiple adversities in healthy children and were published in English. A total of 103 ACE questionnaires were identified in 506 studies. Only 14 of the 103 questionnaires addressed a refugee-specific adversity. Their ability to capture refugee children’s experiences was limited: available questionnaires used a maximum of three items to assess refugee-specific adversities, covering only a fraction of forms of adversities relevant to refugee children. Psychometric characteristics were rarely reported. In addition, only two ACE questionnaires were used within a refugee population. With the tools currently available, it is not possible to comprehensively assess the exposure to and severity of the adversities faced by refugee children. The perpetuation of ongoing crises necessitates assessing refugee children's adversities to understand how their well-being is affected and to identify children at risk.

Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.

This study analysed through the perspective of networks the association between physical activity (PA), sedentary behaviour (SB), and cardiovascular risk factors in overweight low-income schoolchildren from the perspective of complex systems. Methods: The sample consisted of 41 overweight children between 6 and 10 years old (56% girls). PA and SB were analysed by accelerometer, and the measures of cardiovascular factor risk were: anthropometric and hemodynamic measurements, body fat, lipid profile and glucose, cardiorespiratory fitness (CRF), left ven-tricular mass (LVM), and Sokolov-Lyon. Network analysis with Boot-strap-1000 was performed to analyze the association between PA, SB and the cardiovascular risk factors. Results: Moderate to vigorous PA was positive related with Waist circumference (WC; 0.499), HDL-C (0.307), and CRF (0.276), and negatively associated with BMI (-0.251) and Fat (-0.341). For SB, positive associations were seen with WC (0.326), CRF (0.296), LVM (0.250) and Sokolov (0.215). Adicionalment, the centrality indicators highlighted WC as the most important variable in the network. Conclu-sion: Interventions that aim to mitigate the harmful effects of obesity on cardiovascular risk factors in overweight children should consider WC as an important variable in of system.

Novel treatment strategies are emerging for rare, genetic diseases, resulting in clinical trials that require adequate biomarkers for the assessment of the treatment effect. For enzyme defects, biomarkers that can be assessed from patient serum, such as enzyme activity, are highly useful, but the activity assays need to be properly validated to ensure a precise, quantitative measurement. Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by the deficiency of the lysosomal hydrolase aspartylglucosaminidase (AGA). We have here established and validated a fluorometric AGA activity assay for human serum samples from healthy volunteers and AGU patients. We show that the validated AGA activity assay is suitable for the assessment of AGA activity in the serum of healthy controls and AGU patients, and it can be used for diagnostics of AGU and, potentially, for following a treatment effect.

Introduction: The aim of this study was to prospectively evaluate parents’/guardians’ late recall of surgical procedures and risks of elective surgery after pre-operative interview with surgeons. Materials and Methods: All parents/guardians of patients <18 years of age undergoing elective procedures from January 15th to September 1st, 2022, were prospectively enrolled in the study. Before discharge, parents/guardians were asked to complete a questionnaire regarding the duration of the consent procedure, duration of the interview, quality of the informative handouts, and their ability to recall the type of disease, type of surgical procedure, and surgical risks. Answers were graded from 1 to 4. Results: One hundred and two questionnaires were returned. In all cases, informed consent was obtained between 24 and 72 hours prior to surgery. The following responses were collected: 98/102 (96%) parents/guardians reported that the duration of the consent process was adequate; 95/102 (93%) reported that the handouts were fully informative, and 7/102 (7%) reported that they were partially informative regarding explanation of the disease and surgical procedure; regarding complications, 93/102 (91%) perceived the handouts to be fully/partially informative, while 4/102 (4%) perceived the handouts to be poorly/non-informative, and 5/102 (5%) did not provide a response; 94/102 (92%) stated that they remembered the pathology, but only 87/94 (93%) recalled it correctly; 90/102 (88%) stated that they remembered the type of procedure, but only 76/90 (84%) recalled it correctly; and 53/102 (52%) stated that they remembered the surgical risks, but only 20/53 (38%) could recall more than one complication. Conclusions: Late recall of surgical complications by parents was poor despite the high perceived quality of the surgical risk handouts and medical interview.

Worldwide, diarrhoea in children under-five years of age is the second leading cause of death. Despite having high morbidity and mortality, diarrhoeal diseases can be averted by simple and cost-effective interventions. The Integrated Management of Childhood Illness (IMCI) has proposed the use of Oral Rehydration Salt (ORS) and zinc together with adequate food and fluid intake for the management of acute non-dysenteric watery diarrhoea in children. In the past, few studies examined the determinants of adherence to diarrhoea case management. Therefore, this study measured the determinants of therapeutic and dietary adherence to diarrhoea case management using the third and fourth wave of Pakistan Demographics & Health Surveys (PDHS) datasets. Data from 4,068 children between 0 to 59.9 months with positive history of diarrhoea were included, while data on children with dysentery, severe dehydration, and co-morbid condition was excluded. This study reported therapeutic adherence in less than 10% of children in Pakistan, while dietary adherence was reported in 39.2% of children (37.7% in 2012-2013 ~ 40.7% in 2017-2018). A significant improvement in therapeutic (0.8% in 2012-2013 ~ 8.1% in 2017-2018) and dietary adherence (37.7% in 2012-2013 ~ 40.7% in 2017-2018) was reported in the 2017-2018 survey, compared to the 2012-2013 survey. In general, children over the age of one year (compared to children <1 year) and of the richer/richest socioeconomic class (compared to poorest/poorer socioeconomic class) have showed higher therapeutic and dietary adherence. Therapeutic and dietary adherence among diarrhoeal children can be improved by increasing the awareness and accessibility of ORS, zinc, and essential foods.