Current Pediatric Reviews - Online First
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How not to Misdiagnose the Mild Forms of Mucopolysaccharidosis and Juvenile Idiopathic Arthritis
Available online: 04 July 2025More LessAimsThe similarity between mucopolysaccharidosis (MPS) patients and juvenile idiopathic arthritis (JIA) leads to ineffective and needless anti-rheumatic treatment and delayed initiation of enzyme-replacement therapy, the early start of which is crucial for diminishing the disease progression and yielding better outcomes
BackgroundThe prevalence of joint involvement in the attenuated forms of MPS leads to the JIA misdiagnosis, especially in patients without distinctive facial dysmorphic features.
ObjectiveOur study aimed to compare mild forms of MPS and JIA and create a diagnostic score helping to differentiate both conditions.
Methods41 patients with mild forms of different types of MPS and 255 JIA patients with polyarthritis were included in the retrospective study. The routine clinical and laboratory features were used for the comparison analysis.
ResultsThe main features of the MPS cohort were younger age at the disease onset, lower weight and height lower inflammation, and higher number of affected joints compared to JIA patients and involvement in the organs and system, specific for MPS. The majority of the patients had similar C-reactive protein levels. At least two extra-articular features with polyarticular involvement were the main discriminating factors for both conditions. The sum (>38) of the following criteria:ESR< 12 mm/h (38 points), growth delay (height ≤ -2.0 SD; 20 points), age of joint involvement < 1.0 years (24 points), male sex (15 points), and involvement of both elbows with limited range of motion (29 points) can help in the differentiation If a patient had no extra-articular features, typical for MPS. The specificity and sensitivity of this model are 91.0% and 92.7% respectively.
ConclusionThis diagnostic algorithm might increase the suspicion of MPS and should be added to routine testing not miss the mild form of MPS inside JIA. Early diagnosis of mild cases allows for the initiation of treatment in patients with MPS at an earlier stage, which can significantly improve their daily functioning and quality of life.
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The Relationship Between Hypotonia and Vestibular Dysfunction in Young Children: A Scoping Review
Available online: 25 June 2025More LessObjectiveTo explore the prevalence and characteristics of infantile idiopathic hypotonia in the literature and investigate a potential association with vestibular dysfunction in young children.
MethodsA scoping review was conducted following the Joanna Briggs Institute (JBI) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) standards. Literature was searched across MEDLINE, EMBASE, and Web of Science. Google Scholar, GreyNet International, and trial registers were searched for grey literature. Eligible articles were required to report features of children with idiopathic hypotonia or a predefined synonym.
ResultsOf 4,174 screened articles, 16 met the inclusion criteria. Eleven studies focused on various underlying causes of hypotonia and comprised 1150 hypotonic children, of which 24% remained undiagnosed. The remaining studies delved into the characteristics of idiopathic hypotonic children and described different developmental challenges in these children.
DiscussionClumsiness and poor coordination were commonly reported, and therapy, aiming to enhance muscle strength, coordination, and balance, was often recommended, yet none of the included articles explored vestibular dysfunction.
ConclusionDespite diagnostic advancements, the underlying cause of hypotonia remains unidentified in some children. While similarities exist between hypotonic children and children with vestibular dysfunction, none of the reviewed studies explored vestibular dysfunction, warranting further investigation.
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Netherton Syndrome Perspectives
Available online: 19 June 2025More LessNetherton syndrome (NS), also known as Comèl-Netherton syndrome, is a rare disorder of cornification resulting from pathogenic variants in the Kazal type 5 (SPINK5) gene encoding serine protease inhibitor LEKTI. NS is characterized by the triad of congenital ichthyosiform erythroderma (CIE)/ichthyosis linearis circumflexa (ILC), trichorrhexis invaginata (TI), and atopic diathesis. Due to the severity of pathogenesis and variability in clinical presentations, the management of NS poses significant therapeutic challenges, which often require a multidisciplinary approach. Current treatment modalities predominantly consist of topical interventions and supportive measures. With an improved understanding of NS pathophysiology, emerging literature has suggested novel systemic therapeutic options for NS, which include repurposed biologics like targeted inhibitors and intravenous immunoglobulins, but there remains a paucity of literature regarding their clinical outcomes. Although often cited among dermatologists and allergists, the condition is rare in Hong Kong and Singapore, and most physicians have not managed any case. This review suggests that NS may be underestimated clinically. We aim to raise awareness for clinicians in the specific clinical characteristics and pathophysiology of NS to decide tailor-made treatment plans and improve patient outcomes.
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The Association between Prenatal Antibiotic Use and the Risk of Autism Spectrum Disorders among Children: An Updated Meta-Analysis
Authors: Azam Maleki, Helen Behmanesh and Ensiyeh JenabiAvailable online: 14 May 2025More LessObjectiveStudies on prenatal antibiotic use and Autism Spectrum Disorder (ASD) risk have yielded inconsistent results.
AimThis study aimed to resolve these discrepancies by conducting a meta-analysis on the relationship between prenatal antibiotic use and ASD in children.
MethodA comprehensive search was conducted in three main databases: PubMed, Scopus, and Web of Science, up to August 1, 2024. The analysis employed random-effect models to estimate effect sizes, including hazard ratios (HR) and odds ratios (OR). Publication bias was assessed using Begg's test and Egger's regression test. Subgroup analyses explored variations in the association based on the trimester of pregnancy. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).
ResultsIn this meta-analysis, which included twelve studies with a total population of 5,065,060, prenatal antibiotic use was associated with an increased risk of Autism Spectrum Disorder (ASD). The estimated HR for this risk was 1.08 (95% CI: 1.05, 1.12), and the OR was 1.16 (95% CI: 1.09, 1.23), with no detected heterogeneity among studies. The analysis found no publication bias. Significant associations were observed for each trimester: first trimester (HR: 1.11; 95% CI: 1.04, 1.18), second trimester (HR: 1.10; 95% CI: 1.06, 1.14), and third trimester (HR: 1.09; 95% CI: 1.01, 1.18).
ConclusionThe analysis showed that prenatal antibiotic use is a risk factor for ASD. Prenatal antibiotic use was associated with an increase in the risk of ASD across all trimesters of pregnancy. Future research should focus on elucidating the mechanisms underlying this association by examining the effects of specific antibiotic classes, dosages, and timing during critical developmental periods. Longitudinal studies with comprehensive control for confounding factors are essential for strengthening causal inferences and guiding clinical recommendations regarding antibiotic use during pregnancy.
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Effects of Breast Milk or Supplemented Formula Milk on Fecal Metabolomic Profile
Available online: 28 April 2025More LessBreast milk is the best option for the nutritional needs of an infant. In situations where breastfeeding is contraindicated, donor human milk and formula milk are suggested as alternatives. This study highlights findings from two studies that evaluated how different dietary patterns (standard formula, post-biotic fermented formula, and breast milk) affected the intestinal microbiota and metabolome of late preterm and full-term infants. The metabolome of late preterm newborns showed a higher presence of metabolites-such as azelaic acid, N-acetylglucosamine-6- sulfate, and 13(S)-hydroperoxylinolenic acid-in those fed postbiotic-fermented formula, similar to breastfed full-term newborns. The fecal metabolites of breast milk and substitute feeding systems are comparable in these preliminary studies, confirming the effectiveness of formula preparations as breast milk substitutes. Furthermore, newborns fed with postbiotic-supplemented formula or breast milk had several similarities in fecal metabolites. The addition of postbiotics to formula milk appears to be more efficient than standard formula milk and is considered a better alternative to breast milk.
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Special Health Care Needs in Internationally Adopted Children: Prevalence of Chronic Conditions and Interesting Origin-correlated Risk Factors
Authors: Signorelli Benedetta, Lisi Catiuscia, Galli Luisa and Chiappini ElenaAvailable online: 17 April 2025More LessIntroductionThe Federal Maternal and Child Health Bureau defines Children with special health care needs (CSHCN) as those who have, or are at increased risk for, chronic physical, developmental, behavioral, or emotional conditions, and require health and related services beyond what is generally required by other children. More than half of the entire Italian internationally adopted children (IAC) population has special needs. This monocentric retrospective study aims to describe the demographic features and prevalence of several chronic conditions in a large cohort of IAC.
MethodsBetween 1 January 2009 and 31 October 2023, we consecutively enrolled all IAC referred to Anna Meyer Children’s University Hospital, in Florence. This process followed a standardized operative protocol developed internationally. Then, univariate logistic regression analyses were performed.
ResultsAmong 2694 IAC, 315 children (11.89%) were found to be affected by a chronic condition. Asia appears to have 101/561 (18.00%) prevalence of diseases in the total number of IAC from this region of origin, followed by Eastern Europe with 135/1030 (13.11%), Latin America 63/598 (10.54%) and Africa 16/435 (3.68%). The countries of origin with higher prevalence of chronic conditions were China (57.75%), India (15.89%), Russia (15.44%), and Ukraine (13.79%). Children adopted from China and India have a high prevalence of malformations (p = 0.016), while children adopted from Russia accounted for 69.77% of the total fetal alcohol syndrome affected in our cohort. Mental and behavioral disorders appear significantly more prevalent in children from Latin America (p = 0.015), whereas endocrinological disorders predominate in children from Africa (p = 0.014). High rates of precocious puberty were recorded in Asia (p = 0.018) and Africa (p = 0.001) in comparison with the other regions of origin.
ConclusionA revision of the current definition of special needs for adoptive purposes is recommended. Italian screening of the adopted child could be tailored considering the country of origin, and the study of mental health should definitively become part of it.
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Parvovirus B19 Intrauterine Infection and Cerebral Cortical Dysplasia: A Case Report
Available online: 14 April 2025More LessBackgroundIntrauterine parvovirus B19 infection usually causes fetal anemia, hydrops, and stillbirth. Less commonly, central nervous system injuries have also been described.
Case PresentationWe report an atypical case of severe brain injury with diffuse malformation of cortical development and severely immature gyration in a preterm infant with profound fetal anemia and hydrops due to congenital parvovirus B19 infection. The fetus was treated with multiple intrauterine transfusions. Postnatal magnetic resonance imaging of the brain showed extensive encephalomalacia with severe volume loss of both hemispheres, associated with a deranged, markedly immature gyration.
ConclusionThis case provides the first description of severe delay in brain maturation in intrauterine parvovirus B19 infection and represents evidence of a possible teratogenic effect of parvovirus B19 on the brain tissue.
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The Role of Immune Markers in Predicting Infectious Complications in Children with Congenital Heart Defects
Available online: 26 March 2025More LessThe literature review presents data from a limited number of available studies conducted over the last two decades on immunological deficiency in congenital heart defects (CHDs), which is the cause of frequent infectious complications before and after cardiac surgery. Several studies based on screenings at various levels indicate the presence of primary and secondary immunodeficiency in CHDs, in particular about 13 genetic syndromes in which CHD is combined with immunodeficiency. The available data suggests a greater severity of immunological disorders in patients with critical CHDs, cyanotic CHDs, and conotruncal defects with T-cell dysfunction and deficiency of immunoglobulins (especially the IgG class, mainly IgG4) than in patients with shunts and obstructive defects. To identify defects in the T- and B-cell components of the immune system, quantification of the DNA of T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs)-by-products of the maturation of T- and B-cell receptors-has proven helpful in the world practice of neonatal screening. It allows the evaluation of a number of functionally mature T- and B-cells. In Russia, however, its widespread use started only in 2023. Data on the use of this assay in infants with CHDs are represented by isolated case reports. In Russia, a combination of CHD and primary immunodeficiency was found in 37% of cases in the Sverdlovsk Region. We conducted our own study of 200 children with CHD; 5% of cases were syndromic forms of CHD. 48.5% of children were admitted to the cardiac surgery clinic in critical condition. A decrease in the TREC level was detected in 23.5% of cases, including all children with syndromic CHD. In the group of patients with immunological disorders, there were significantly more children with cyanotic CHD, children admitted in critical condition, and children with conotruncal defects. Infectious complications in the postoperative period (sepsis, pneumonia, tracheobronchitis, postoperative wound infection) were observed significantly more often in 47 children with reduced TREC levels compared to children with normal TREC levels (P = .00000, in 36% and 3.6%, respectively). The analysis of publications confirms the prognostic value of TREC and KREC screening for targeted preoperative preparation to reduce postoperative complications and decrease the risk of mortality in CHDs.
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Parental Knowledge and Attitudes Towards Antibiotic Resistance in Children: A Review Article
Authors: Majd Masadeh, Sabariah Noor Harun, Tareq Mukattash and Nasr AlrabadiAvailable online: 12 February 2025More LessAntibiotic misuse among children continues to be one of the major critical public health issues worldwide, particularly in developing countries such as Jordan. Incorrect antibiotic use is hugely influenced by parents' knowledge and attitudes on the subject at hand. This review, therefore, seeks to establish the current state of parental knowledge and attitudes toward antibiotics in Jordanian children, with particular emphasis on those gaps in awareness and knowledge that underpin the inappropriate use of antibiotics. Despite prescription regulations, many still depend on over-the-counter purchases, usually due to misconceptions about the efficiency of antibiotics in viral infections or a lack of insight into the risks of misuse. The results strongly suggest that focused educational programs are needed to improve parents’ knowledge of prudent antibiotic use. It integrated an analysis of the socio-cultural factors affecting parental decisions and recommended improvising the public health strategies in their fight against antibiotic resistance. The study concluded that emphasis must be laid on both regulatory enforcement and public awareness about appropriate antibiotic use in pediatric care to bring about better health outcomes in Jordanian children.
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Aberrant Expressions of EDNRB and EDN3 in a Multifactorial Hirschsprung Disease
Available online: 22 January 2025More LessBackgroundHirschsprung disease (HSCR) is a multifactorial disorder due to the enteric nervous system (ENS) development failure. At least 35 genes have been responsible for HSCR, including EDNRB and EDN3. Here, we aimed to determine the EDRNB and EDN3 expressions effects in HSCR subjects.
MethodsOur study analyzed EDNRB and EDN3 expressions in the colon of HSCR subjects and controls by a quantitative PCR. The EDNRB and EDN3 expressions were analyzed by the Livak method (2-ΔΔCT).
ResultsTwenty-seven HSCR patients and 20 controls were ascertained. EDNRB and EDN3 expressions downregulated was found in ganglionic and aganglionic HSCR than control colons (EDNRB: ΔCT 6.78 ± 1.38 vs. 1.71 ± 2.79; p = 0.0001 (ganglionic); ΔCT 4.41 ± 1.63 vs. 1.71 ± 2.79; p = 0.0005 (aganglionic); and EDN3: ΔCT 7.60 ± 1.93 vs. 1.81 ± 2.89; p = 0.0001 (ganglionic); ΔCT 9.72 ± 4.32 vs. 1.81 ± 2.89; p = 0.0001 (aganglionic)). A significant difference in EDNRB and EDN3 expressions was also noted between the HSCR colon: ganglionic vs. aganglionic segment (p = 0.00002 and 0.017).
ConclusionWe report the downregulated EDNRB and EDN3 expressions in HSCR subjects, indicating EDNRB/EDN3 expressions have a significant responsibility in HSCR pathogenesis. Nevertheless, we further clarify the complexity of the development of ENS.
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GeneXpert MTB/RIF Ultra in Pediatric Tuberculosis: How Disease Characteristics Modify Test Performances
Authors: Domenico Pace, Roberta Pellegrino, Irene Dalpiaz, Marco Renni, Luisa Galli and Elena ChiappiniAvailable online: 06 January 2025More LessIntroductionThe diagnosis of pediatric tuberculosis (TB) is challenging, due to the lower sensitivity of microbiological tests, such as culture and microscopy, compared to their performance in adult cases. Guidelines have introduced molecular tests, including GeneXpert MTB/RIF and GeneXpert MTB/RIF Ultra. These tests use a real-time polymerase chain reaction method and provide information on M. tuberculosis detection and drug-resistance-associated mutations in less than 2 hours. This retrospective single-center study aimed to evaluate the accuracy of GeneXpert and GeneXpert Ultra for the diagnosis of pediatric TB.
MethodsThis retrospective study was conducted on a total of 95 children diagnosed with probable or confirmed TB disease (74 diagnosed with pulmonary TB, 21 with extrapulmonary TB), who referred to the infectious disease unit at Meyer Children’s Hospital in Florence, Italy, and tested with GeneXpert MTB/RIF or GeneXpert Ultra, from 2013 to 2023.
ResultsGeneXpert and GeneXpert Ultra demonstrated a detection rate of 0.357 (95% CI 0.180 to 0.535) and 0.537 (95% CI 0.417-0.657), respectively. No child was tested with both tests. Patients’ characteristics, including age and sex, did not significantly influence the test's performances. Notably, GeneXpert Ultra had a significantly higher detection rate in children with extrapulmonary TB (0.813, 95% CI 0.621 to 1.004) compared to that in children with pulmonary TB (p = 0.020). Gastric aspirate was the most tested specimen. Specimens that did not require invasive procedures for collection (including stool) yielded poor results. GeneXpert and GeneXpert Ultra permitted rapid evaluation of genotypic drug-sensitivity testing (DST), even though limited to rifampicin resistance, making necessary confirmation through phenotypic DST (performed on culture).
ConclusionThe introduction of GeneXpert and GeneXpert Ultra improved TB diagnosis in children, by providing microbiological information in a short time, complementing results from culture, which remains the reference test in pediatric TB diagnosis.
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Primary Renal Neuroblastoma: A Case Report and Review of the Literature
Authors: Rejin Kebudi, Dilşad Koca and Ulku Miray YildirimAvailable online: 02 January 2025More LessIntroductionNeuroblastoma is the most common extracranial solid tumor found in childhood.
Case RepresentationPrimary renal neuroblastoma has been reported in the literature as case reports. Almost all cases had a preliminary diagnosis of Wilms tumor and were diagnosed as neuroblastoma after nephrectomy. Renal localized neuroblastoma may not be distinguished radiologically from Wilms tumor.
DiscussionWe report a case of a 9-month-old infant with primary intrarenal neuroblastoma and provide a literature review. The definitive differential diagnosis of some renal masses is both radiologically and clinically challenging.
ConclusionIn such cases, the input of a multidisciplinary team, including the oncologist, surgeon, and radiologist, is invaluable in deciding on a biopsy or nephrectomy.
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Cardiology Consult for the General Pediatrician after Cardiac Manifestations from a SARS-CoV-2 Infection
Available online: 02 October 2024More LessThe novel Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, created a need for evidence-based guidelines for the evaluation, management, and follow-up after infection. Data have become rapidly available, creating a challenge for medical providers to stay abreast of the ever-evolving recommendations. This document, written collaboratively by pediatric cardiovascular experts, pediatricians, and sports medicine specialists, is focused on SARS-CoV-2-related pediatric cardiac manifestations. It aims to provide a systemic review of high-yield literature related to all cardiovascular entities as a tool for primary pediatric clinicians to utilize as they consider the cardiac consequences of acute SARS-CoV-2 infection, MIS-C, vaccine-related myocarditis, return-to-play, and long COVID-19 syndrome.
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