Pediatric Reports

Background: Anemia is common in patients with nephrotic syndrome (NS) for various reasons. Furthermore, anemia can occur in patients with chronic kidney disease (CKD) predominantly owing to inappropriately low erythropoietin (EPO) production relative to the degree of anemia. However, erythrocytosis is uncommon in patients with NS and advanced CKD who are not treated with exogenous erythropoietin stimulating agents, and when present, will necessitate exploration of the other etiologies. Case summary: Here, we describe an 8-year-old girl with erythrocytosis in association with NS and advanced CKD. The patient was found to have erythrocytosis during the evaluation for hypertensive urgency. She also had nephrotic range proteinuria without edema. Serum hemoglobin and hematocrit were 17 gm/dL and 51%, respectively, despite hydration. Renal function test showed an estimated glomerular filtration rate of 30 mL/min/1.73 m². There was mild iron deficiency anemia with serum iron saturation of 18%. Serum EPO level was normal. Urine EPO was not measured. Renal biopsy showed evidence of focal segmental glomerulosclerosis. Genetic testing for NS showed mutations in podocyte genes: NUP93, INF2, KANK1, and ACTN4. Gene sequence analysis of genes associated with erythrocytosis showed no variants in any of these genes. She required chronic dialysis ten months later and, subsequently, a renal transplantation 14 months after the initial presentation. Conclusion: Since the serum EPO level was normal, an increased sensitivity to EPO is the most probable mechanism of erythrocytosis. The unusual association of erythrocytosis in patients with NS and advanced CKD needs to be studied further in larger studies. Full article

Background: Attention deficit hyperactivity disorder is the most common childhood psychiatric disorder. Current treatment strategies do not provide a convincing improvement on overall functioning, and further, reciprocity between ADHD and attachment has been suggested. This suggests that we do not fully comprehend the mechanisms of the disorder. This study was part of a larger project investigating factors of potential importance when a child is diagnosed with ADHD. Aim: In this current study we aimed to gain a clearer understanding about whether the mothers experienced the diagnostic process and treatment as helpful. Method: Sixty children newly diagnosed with ADHD and their mothers were included three years prior to this study. Fifty-two (87%) completed a survey about their experience with the diagnostic process and the years after in the psychiatric system and the secondary healthcare sector. Forty-three had also participated in an attachment interview in the original study and answered questions about this. Discussion: The follow-up questionnaire was based on conversations with the mothers was not meant to be used as a quantitative measure. However, one point to take is that the mothers did often not feel the help offered to be sufficient. In our opinion, this underlines that we are still far from understanding what ADHD is and what causes the differences in developmental trajectories as well as how differences in etiological factors may call for more customized approaches in treatment strategies. Full article

We present a case of a transient acquired zinc deficiency in a breast-fed, 4-month-old-male prematurely born infant, with acrodermatitis enteropathica-like symptoms such as crusted, eroded, erythemato-squamous eruption in periorificial and acral patterns. The laboratory investigations showed low zinc levels in the infant’s and the mother’s serum and in the mother’s milk; genetic analysis did not show any mutation in the SLC39A4 gene, involved in acrodermatitis enteropathica. Acquired zinc deficiency is often found in premature infants because of their increased requirement, the low serum and milk zinc levels in breastfeeding women being also an important risk factor, as in this case. A prompt zinc supplementation is essential for the good prognosis of the disease. Full article

Objective: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder diagnosed in increasing proportions of children and adolescents. The psychostimulant methylphenidate has been considered the first-line pharmacological treatment for children and adolescents with ADHD for more than 60 years. Considering recent publications on methylphenidate for ADHD, we here give an overview of its effects in children and adolescents with ADHD, elicited by a well-disputed Cochrane review and narratively synthesise the evidence in the field. Method: We searched for systematic reviews and meta-analyses that investigated methylphenidate as an intervention for children and adolescence with ADHD compared with placebo or no treatment. We assessed the quality of the evidence using AMSTAR II. Results: We found 24 eligible systematic reviews and meta-analyses of which 11 were rated as high- quality evidence according to AMSTAR II. The evidence claiming that methylphenidate is beneficial in treating children and adolescents with ADHD was of very low certainty. The underreporting of adverse events in randomised clinical trials may impede an adequate depiction of the balance between benefits and harms. Conclusions: It appears that there is uncertain evidence on group-level to support the claim that methylphenidate is beneficial in treating children and adolescents with ADHD. Future randomised clinical trials and systematic reviews should include individual participant data, which would allow us to assess intervention effects across modifiers, like age, sex, ADHD subtypes, comorbidities, and dose. Full article

Background: To describe trends and clinical experiences in applying commercial pharmacogenetic testing among pediatric patients with neuropsychiatric disorders. Methods: Demographic and clinical data of patients receiving GeneSight^® testing from January 2015 to November 2016 at an urban pediatric hospital were retrospectively extracted from medical charts. Outcome data included pharmacogenetic test results and medication prescriptions before and after the test. Results: A total of 450 patients (12.1 ± 4.3 years) diagnosed with anxiety disorder, attention deficit hyperactivity disorder, developmental disorders including autism, and/or a mood disorder received testing, and 435 of them were prescribed medications. Comparing data before and after testing, the total number of psychotropic prescriptions were reduced by 27.2% and the number of prescribed medications with severe gene-drug interactions decreased from 165 to 95 (11.4% to 8.9% of total medications prescribed). Approximately 40% of actionable genetic annotation were related to CYP2CD6 and CYP2C19. Patients of Asian descent had significantly higher likelihood than other races of being classified as poor to intermediate metabolizers of antidepressants, mood stabilizers, and antipsychotics (p = 0.008, 0.007, and 0.001, respectively). Diagnoses, including autism spectrum disorder, were not associated with increased risks of severe gene-drug interactions. Conclusions: Pharmacogenetic testing in child and adolescent psychiatry is currently based on few clinically actionable genes validated by CPIC and/or FDA. Although this approach can be moderately utilized to guide psychotropic medication prescribing for pediatric patients with psychiatric disorders, clinicians should cautiously interpret test results while still relying on clinical experience and judgment to direct the final selection of medication. Full article

Immunoglobulin A (IgA) vasculitis is the most common systemic vasculitis in the pediatric population. We present the case of a patient with IgA vasculitis with nephritis who developed cytomegalovirus (CMV) infection followed by Mycobacterium tuberculosis infection. In the literature, there are a few cases of IgA nephropathy accompanied by reactivation of CMV or tuberculosis. To the best of our knowledge, this is the first reported case of IgA vasculitis complicated by both CMV reactivation and tuberculosis. It is important to detect infections in patients with IgA vasculitis because they can induce and exacerbate the symptoms of the disease. Effective antimicrobial treatment facilitates the management of proteinuria and slows down the decline of renal function. Immunosuppressive therapy is a risk factor for reactivation of latent infections and makes patients more susceptible to its generalized and complicated course. This can be prevented by actively screening for hidden sites of infection. Full article

A growing number of children and adolescents play video games (VGs) for long amounts of time. The current outbreak of the Coronavirus pandemic has significantly reduced outdoor activities and direct interpersonal relationships. Therefore, a higher use of VGs can become the response to stress and fear of illness. VGs and their practical, academic, vocational and educational implications have become an issue of increasing interest for scholars, parents, teachers, pediatricians and youth public policy makers. The current systematic review aims to identify, in recent literature, the most relevant problems of the complex issue of playing VGs in children and adolescents in order to provide suggestions for the correct management of VG practice. The method used searches through standardized search operators using keywords related to video games and the link with cognition, cognitive control and behaviors adopted during the pandemic. Ninety-nine studies were reviewed and included, whereas twelve studies were excluded because they were educationally irrelevant. Any debate on the effectiveness of VGs cannot refer to a dichotomous approach, according to which VGs are rigidly ‘good’ or ‘bad’. VGs should be approached in terms of complexity and differentiated by multiple dimensions interacting with each other. Full article

Cancer children experience long periods of hospitalization, which are associated with limited performance in several developmental domains and participation restrictions in age appropriate occupations. Fine motor abilities represent building blocks in performing daily life skills and have been found to be closely connected with later academic success. Moreover, medical and psychological sequelae for cancer inpatients may result in diminished daily activities functioning, poor perceived health related quality of life (HRQOL), and increase the likelihood of long-term impairments. This study examines the variations in the occupational performance of children hospitalized for acute lymphoblastic leukemia (ALL) after their participation to a stimulation program designed to enhance fine motor skills. Parents reported significant gains in children’s motor functioning, a slight improvement in overall occupational performance related to an increase in the area of productivity and self-care, and a better quality of life perception following the stimulation activities. Feasibility of the stimulation program in a health care setting are discussed evaluating its benefits for cancer children and their families. Full article

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease. Full article

Hypertransaminasemia in patients with Kawasaki disease (KD) is reported to be transient. Here, we describe a child with an atypically protracted course of liver tests abnormalities and review the inherent literature. The patient was hospitalized at age 7-months for isolated hypertransaminasemia detected during a classical KD diagnosed 3 months before, and persistent since then. KD clinical evolution had been favorable, with rapid response to acetylsalicylic acid and intravenous immunoglobulins. Liver enzymes however remained persistently elevated with a fluctuating pattern (ALT > AST levels; peak of AST 186 IU/L and ALT 240 IU/L). During follow-up, the main causes of liver dysfunction had to be excluded through appropriate and extensive laboratory investigations. Transaminases values become steadily normal only 7 months after the acute presentation of KD. Conclusions: Our report shows that an atypically protracted courses of KD-related hypertransaminasemia above the previously reported temporal limits should be taken into account during the stepwise diagnostic approach to the patient’s liver dysfunction. Insidious acetylsalycilic acid-hepatotoxicity warrants consideration in the differential diagnosis. Full article

Infantile hemangiomas are common benign vascular tumors but are rarely found in an intracranial location. Our literature review identified 41 reported cases. There is no general consensus on management of these rare lesions and until recently, treatment was limited to surgery or pharmacological management with steroids or interferon. Although beta-blockers have been widely prescribed in the treatment of cutaneous infantile hemangiomas since 2008, their use in the treatment of intracranial infantile hemangiomas has been minimal. We present a case of infantile hemangioma affecting the right orbit, associated with intracranial extension, causing intermittent right facial nerve palsy. The patient achieved an excellent outcome following combined treatment with oral propranolol and topical timolol maleate 0.5%, with complete regression of the lesion by 4 months. We conclude that beta-blockers are a safe and effective treatment of intracranial infantile hemangiomas and can be employed as first-line management of these lesions. Full article

Frailty (FI) and metabolic syndrome (MS) are each associated with adverse health outcomes. A relationship between FI and MS has previously been described in adults. We considered the prevalence of a metabolically unhealthy phenotype (MUP) in malnourished children with neurological impairment and in subjects with obesity in comparison to a group of elderly individuals at risk of FI, and we did so in order to define the potential similarities that may underline the risk of FI in specific children. We considered 50 undernourished (defined as having a body mass index of BMI ≤ 2, standard deviation score, SDS, according to World Health Organization) disabled children; 50 children with obesity (BMI ≥ 2 SDS); 50 children who were a normal weight (−1 SDS ≤ BMI ≤ +1 SDS); 21 patients who were >75 years old. MUP was defined as the presence of at least one of the following risk factors: hypertension, hyperglycemia or diabetes, hypercholesterolemia, and hypertriglyceridemia. In children with a disability and obesity, a higher prevalence (p < 0.001) and risk (disability OR 54.88, obesity OR 13.37) of MUP was noted compared to children of a normal weight. Compared to elderly patients, the prevalence of MUP did not differ in disabled children. On the contrary, MUP was lower in children with obesity (p < 0.001) and in pediatric subjects of a normal weight (p < 0.01). MS might play a key role in “pediatric” frailty. The extremities of the aging process and malnutrition are likely key factors in the development of FI. A multidisciplinary approach to FI may represent an important milestone for pediatric care. Full article

While the Coronavirus Disease 2019 (COVID-19) pandemic continues to wreak havoc across the nation and the globe as one of the most significant global health crises of our time, recent attention has been turned to the effects of COVID-19 on pregnancy and the puerperium. Although most cases have been asymptomatic, for some patients, the disease may be accompanied by serious complications such as pneumonia, acute respiratory distress, multi organ failure, and death. Several case studies have noted that patients with co-morbidities are at a significant risk of these complications. In a recent systematic review and meta-analysis, authors conclude that cardiovascular disease was associated with increased composite poor outcome in patients with COVID-19. The following case report highlights the multi-system complications and severity of symptoms that can take place after childbirth in a patient with co-morbid obstetric and prenatal conditions and an initially asymptomatic COVID-19 infection. Full article

Age-groups are commonly implemented in education and sports in order to provide fair and equal opportunities. Various studies, however, have shown a competitive advantage for early born children over their relatively younger peers, which is referred to as relative age effect. The present study examined differences in various components of physical fitness in Austrian elementary-school children. A total of 18,168 children (51% boys) between 6 and 11 years of age provided valid data on anthropometric characteristics and physical fitness. Specifically, children completed eight fitness tests that assessed cardiorespiratory endurance, muscular strength and power, speed, agility, flexibility and object control. Across age-specific quartiles, older children were significantly taller and heavier than their younger peers. Older children also displayed better performance for strength and power, speed, agility and object control, while differences in cardio-respiratory endurance were less pronounced. These results highlight the presence of a relative age effect during the elementary school years and emphasize the need to consider individual differences in the evaluation of children’s performance. As all children should be given equal opportunities to engage successfully in physical education and sports, physical education teachers and youth coaches need to be educated on the implications of a relative age effect. Full article

The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way. Full article

(1) Background: The study aims to identify which imaging parameters are necessary for a new correct surgical approach in the study of choanal atresia, and which anatomical findings are essential for correct planning of endoscopic treatment in choanal atresia. (2) Methods: In this retrospective study, 19 patients with choanal atresia had high-resolution multiplanar imaging (14 cases aged ≤1 year and 5 cases aged 1 to 3 years) and 35 patients in the control group similarly distributed by age. Fourteen variables, the most relevant from a surgical point of view, were selected and measured. A comparison was made between the averages of the study group and the different control groups, either directly observed or selected from the literature, using Pearson’s correlation. (3) Results: In 14 out of 26 cases, the differences were statistically significant. There was a correlation between the structures assessed, such as choanal height, rostrum height, and age. (4) Conclusions: Thanks to volumetric reformatting, this work identified and provided the clinician with useful information that helped choose the correct surgical approach. Furthermore, it focused on which imaging parameters are necessary to improve the planning of the surgical correction of choanal atresia. Full article

The COVID-19 pandemic has affected maternal and infant health globally both directly from infection with the SARS-CoV-2 virus and indirectly from changes in health care resulting from social, economic, and health care policies unique to each country. The developing countries have to share the disproportionate burden on maternal and infant health. In this review, we discuss the uncertainties resulting from SARS-CoV-2 infection in pregnancy, vertical transmission of the virus, and its effects on breastfeeding of the newborn. The problems of families and communities caring for mothers with COVID-19 and its impact on breastfeeding in newborns are discussed. The challenges posed by the pandemic have forced us to think and devise innovative solutions, including telemedicine help for antenatal counseling, breastfeeding education, and lactation support. Optimal utilization of resources and technology to find creative solutions at the individual and the community level will help in facilitating maternal–infant bonding soon after birth. Appropriate health care policies to support pregnant and lactating mothers will go a long way in meeting healthy child development goals. Full article

To examine whether BMI-associated genetic risk variants modify the association of intrauterine diabetes exposure with childhood BMI z-scores, we assessed the interaction between 95 BMI-associated genetic variants and in utero exposure to maternal diabetes among 459 children in the Exploring Perinatal Outcomes among Children historical prospective cohort study (n = 86 exposed; 373 unexposed) in relation to age- and sex-standardized childhood BMI z-scores (mean age = 10.3 years, standard deviation = 1.5 years). For the genetic variants showing a nominally significant interaction, we assessed the relationship in an additional 621 children in Project Viva, which is an independent longitudinal cohort study, and used meta-analysis to combine the results for the two studies. Seven of the ninety-five genetic variants tested exhibited a nominally significant interaction with in utero exposure to maternal diabetes in relation to the offspring BMI z-score in EPOCH. Five of the seven variants exhibited a consistent direction of interaction effect across both EPOCH and Project Viva. While none achieved statistical significance in the meta-analysis after accounting for multiple testing, three variants exhibited a nominally significant interaction with in utero exposure to maternal diabetes in relation to offspring BMI z-score: rs10733682 near LMX1B (interaction β = 0.39; standard error (SE) = 0.17), rs17001654 near SCARB2 (β = 0.53; SE = 0.22), and rs16951275 near MAP2K5 (β = 0.37; SE = 0.17). BMI-associated genetic variants may enhance the association between exposure to in utero diabetes and higher childhood BMI, but larger studies of in utero exposures are necessary to confirm the observed nominally significant relationships. Full article

The COVID-19 pandemic has led to an unprecedented closure of schools in terms of duration. The option of school closure, SARS-CoV-2 initially being poorly known, was influenced by the epidemiological aspects of the influenza virus. However, school closure is still under debate and seems unsupported by sure evidence of efficacy in the COVID-19 era. The aim of our narrative review is to discuss the available literature on SARS-CoV-2 spread among children and adolescents, in the school setting, trying to explain why children appear less susceptible to severe disease and less involved in viral spreading. We also tried to define the efficacy of school closure, through an overview of the effects of the choices made by the various countries, trying to identify which preventive measures could be effective for a safe reopening. Finally, we focused on the psychological aspects of such a prolonged closure for children and adolescents. SARS-CoV-2, children, COVID-19, influenza, and school were used as key words in our literature research, updated to 29 March 2021. To our knowledge, this is the first review summarizing the whole current knowledge on SARS-CoV-2 spreading among children and adolescents in the school setting, providing a worldwide overview in such a pandemic context. Full article