Children — Open Access Journal of Pediatrics

Background: Sleep concerns are common in children with autism spectrum disorders (ASD). The impact of poor sleep on cognitive performance in ASD children is not well-established. We investigated the possible correlation between sleep quality in ASD children and cognitive performance. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was administered to examine specific components of non-verbal cognition. Methods: The Children’s Sleep Habits Questionnaire (CSHQ) and actigraphy-measured data from 18 children with diagnosis of ASD were evaluated. Motor planning task (MOT), simple reaction time task (SRT) and the intradimensional/extradimensional shift (IED) of CANTAB were administered. Results: ASD good sleeper (ASD-GS) showed significant better response time for SRT task as compared to ASD poor sleeper (ASD-PS) based on CSHQ score. Parameters of bedtime resistance (r = 0.531, p = 0.023), sleep anxiety (r = 0.474, p = 0.047) from CSHQ and actigrapgy dependent (wake after sleep onset (WASO) (r = 0.430, p = 0.024) were significantly correlate with response time of SRT task. Conclusion: We conclude that some signs reflecting the presence of poor sleep in ASD correlate with various aspects of motor output on non-verbal performance tasks. The question is raised whether poor sleep in non-complaining persons with autism should be treated. Full article

Childhood obesity continues to be a major public health concern. Obesity causes various metabolic complications, including insulin resistance, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and cardiovascular disease. However, currently, we have a limited understanding of the pathophysiology in the development of these processes. Extracellular vesicles (EVs) are nano-sized vesicles secreted by different cell types that travel to various organ systems carrying molecular and genetic information. These vesicles have been proposed as a novel intercellular communication mode in systemic metabolic regulation and in several pathophysiologic processes. In particular, recent studies indicate that EVs play a critical role in the pathogenesis of obesity and its metabolic complications. In this study, we reviewed the current literature that supports the role of EVs in the regulation of metabolic homeostasis and pathogenesis of obesity and its associated metabolic complications, with a short discussion about future directions in the EV research field. Full article

Although the most common forms of brain injury in preterm infants have been associated with adverse neurodevelopmental outcomes, existing MRI scoring systems lack specificity, do not incorporate clinical factors, and are technically challenging to perform. The objective of this study was to develop a web-based, clinically-focused prediction system which differentiates severe neurodevelopmental outcomes from normal-moderate outcomes at two years. Infants were retrospectively identified as those who were born ≤30 weeks gestation and who had MRI imaging at term-equivalent age and neurodevelopmental testing at 18–24 months. Each MRI was scored on injury in three domains (intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage) and clinical factors that were strongly predictive of an outcome were investigated. A binary logistic regression model was then generated from the composite of clinical and imaging components. A total of 154 infants were included (mean gestational age = 26.1 ± 1.8 weeks, birth weight = 889.1 ± 226.2 g). The final model (imaging score + ventilator days + delivery mode + antenatal steroids + retinopathy of prematurity requiring surgery) had strong discriminatory power for severe disability (AUC = 0.850), with a PPV (positive predictive value) of 76% and an NPV (negative predictive value) of 90%. Available as a web-based tool, it can be useful for prognostication and targeting early intervention services to infants who may benefit the most from such services. Full article

The present study used nationally representative data from the National Longitudinal Study of Adolescent Health (a.k.a., Add Health) to examine the impact of childhood obesity on young adult educational attainment. In addition to weight status, independent variables included race–ethnicity, immigrant generational status, family socio-economic status (SES), preference for overweight and obese friends in school, school socio-economic and race–ethnic composition, and other important predictors. Educational attainment was measured as a categorical variable with the categories reflecting key educational benchmarks: (1) being a high school graduate; (2) having some college education; and (3) having completed a bachelor’s or higher degree. The results indicate that in general, individuals who were obese as children are less likely to transition from high school to college, and even less likely to obtain a baccalaureate or more advanced degree. In line with the social network hypothesis of the obesity epidemic, we also found that having overweight and obese friends drives down the odds of educational success. Attendance at a higher SES school or a school with a lower percentage of minority students was positively associated with the odds of college attendance and obtaining a baccalaureate. Other important effects included race–ethnicity and immigrant generational status. Full article

Bird Fancier’s Lung (BFL) is a rare, nonatopic immunologic response to repeated or intense inhalation of avian (bird) proteins/antigens found in the feathers or droppings of many species of birds, which leads to an immune-mediated inflammatory reaction in the respiratory system. Although this is the most common type of hypersensitivity pneumonitis (HP) reported in adults, it is one of the classifications of a rare subtype of interstitial lung disease that occurs in the pediatric age group of which few case reports are available in the literature. The pathophysiology of HP is complex; numerous organic and inorganic antigens can cause immune dysregulation, leading to an immune-related antigen–antibody response (immunoglobulin G—IgG- against the offending antigen). Diagnosing BFL in the pediatric age group is challenging due to the history of exposure usually being missed by health care providers, symptoms and clinical findings in such cases being nonspecific and often misdiagnosed during the acute illness with other common diseases such asthma or acute viral lower respiratory tract infection, and the lack of standardization of criteria for diagnosing such a condition or sensitive radiological or laboratory tests. Treatment, on the other hand, is also controversial. Avoidance of the offending antigen could be the sole or most important part of treatment, particularly in acute mild and moderate cases. Untreated cases can result in irreversible lung fibrosis. In this case report, we highlight how children presenting with an acute viral lower respiratory tract infection can overlap with the acute/subacute phase of HP. Early intervention with pulse steroids markedly improves the patient’s clinical course. Full article

While recent increases in our understanding of the biology of neuroblastoma have allowed for more precise risk stratification and improved outcomes for many patients, children with high-risk neuroblastoma continue to suffer from frequent disease relapse, and despite recent advances in our understanding of neuroblastoma pathogenesis, the outcomes for children with relapsed neuroblastoma remain poor. These children with relapsed neuroblastoma, therefore, continue to need novel treatment strategies based on a better understanding of neuroblastoma biology to improve outcomes. The discovery of new tumor targets and the development of novel antibody- and cell-mediated immunotherapy agents have led to a large number of clinical trials for children with relapsed neuroblastoma, and additional clinical trials using molecular and genetic tumor profiling to target tumor-specific aberrations are ongoing. Combinations of these new therapeutic modalities with current treatment regimens will likely be needed to improve the outcomes of children with relapsed and refractory neuroblastoma. Full article

Introduction: Gamma glutamyl transferase (GGT) and uric acid (UA) are reported to be predictive markers in various disorders. It has been reported that these biomarkers can be used to indicate increased risk of mortality in critically ill patients. Herein, we aimed to evaluate the effects of the initial serum GGT and UA levels on the outcomes of patients in the pediatric intensive care unit (PICU) and to investigate if these biomarkers can be used to predict pediatric mortality. Materials and Methods: The relationship between the initial GGT and UA levels and invasive mechanical ventilation (IMV) and noninvasive mechanical ventilation (NIV) support, inotropic drug need, acute renal kidney injury (AKI), continuous renal replacement therapy (CRRT), presence of sepsis, mortality, and hospitalization period were investigated retrospectively. Results: In all, 236 patients (117 males and 119 females) were included in the study. The age distribution of the patients was 1–12 years. There was a statistically significant relationship between GGT levels in the first biochemical analysis performed during admission and inotropic drug use, AKI, duration of hospitalization in intensive care unit, and sepsis. There was a statistically significant relationship between initial UA levels and inotropic drug use, AKI, CCRT, and sepsis. Conclusion: We suggest that initial GGT and UA levels during admission could be used to predict the outcomes of patients in PICU. Full article

Knowledge of the effect of modifiable lifestyle factors in the pediatric multiple sclerosis (MS) population is limited. We therefore conducted a scoping review, following the framework provided by Arksey and O’Malley. Four databases were searched for pediatric MS and modifiable lifestyle factors using index terms and keywords, from inception to May 2018. All quantitative and qualitative primary articles were included and limited to English and full text. Of the 7202 articles identified and screened, 25 full-text articles were relevant to our objective and were included. These articles focused on diet obesity, physical activity, and sleep. In cross-sectional analyses, these lifestyle factors were associated with increased risk of pediatric onset MS (POMS), and increased disease activity. Diet, particularly vitamin D and vegetable intake, was associated with reduced relapse rate. Obesity was linked to increased risk of POMS, and physical activity was associated with reduced relapse rate and sleep/rest fatigue. Thus, available studies of lifestyle related outcomes in pediatric MS suggest specific lifestyle related factors, including obesity, higher vitamin D levels, and higher physical activity may associate with lower disease burden in POMS. Studies reviewed are limited by their observational designs. Future studies with longitudinal and experimental designs may further clarify the role of modifiable lifestyle factors in this population. Full article

Prior to the 1950s, survival from Wilms tumor (WT) was less than 10%. Today, a child diagnosed with WT has a greater than 90% chance of survival. These gains in survival rates from WT are attributed largely to improvements in multimodal therapy: Enhanced surgical techniques leading to decreased operative mortality, optimization of more effective chemotherapy regimens (specifically, dactinomycin and vincristine), and inclusion of radiation therapy in treatment protocols. More recent improvements in survival, however, can be attributed to a growing understanding of the molecular landscape of Wilms tumor. Particularly, identification of biologic markers portending poor prognosis has facilitated risk stratification to tailor therapy that achieves the best possible outcome with the least possible toxicity. The aim of this review is to (1) outline the specific biologic markers that have been associated with prognosis in WT and (2) provide an overview of the current use of biologic and other factors to stratify risk and assign treatment accordingly. Full article

Valid and reliable non-objective assessments of guardian and preschool personnel reports are necessary when estimating young children’s health behaviors. This study examines the test-retest reproducibility of (a) guardian and preschool personnel questionnaires about correlates of preschool-aged children’s energy balance-related behaviors (EBRBs), (b) a screen time diary, and (c) a food frequency questionnaire (FFQ) reported by a guardian. A sample of guardians having preschool-aged children (N = 69) and preschool personnel (N = 61) completed questionnaires twice within a five-week time interval during April–May 2018 in Finland. Intra-class correlations (ICC), kappas, and percentage agreement were calculated to test the test-retest-reproducibility. The guardian questionnaire for correlates of the children’s EBRBs demonstrated mainly moderate to good reproducibility whereas the preschool personnel questionnaire of preschool correlates for children’s EBRBs was mostly good. The reproducibility of the screen time diary was good and FFQ food items showed mostly moderate reproducibility. The reproducibility of the FFQ foods items for vegetables, fruit, and berries was slightly better for the amount consumed than for the frequency of consumption. To conclude, all the instruments are acceptable for use in future studies. Full article

International disparities in outcomes from pediatric solid tumors remain striking. Herein, we review the current literature regarding management, outcomes, and barriers to care for pediatric solid tumors in low- and middle-income countries (LMICs). In sub-Saharan Africa, Wilms Tumor represents the most commonly encountered solid tumor of childhood and has been the primary target of recent efforts to improve outcomes in low-resource settings. Aggressive and treatment-resistant tumor biology may play a role in poor outcomes within certain populations, but socioeconomic barriers remain the principal drivers of preventable mortality. Management protocols that include measures to address socioeconomic barriers have demonstrated early success in reducing abandonment of therapy. Further work is required to improve infrastructure and general pediatric care to address disparities. Full article

Neuroblastoma is the most common extra-cranial solid tumor encountered in childhood and accounts for 15% of pediatric cancer-related deaths. Although there has been significant improvement in the outcomes for patients with high-risk disease, the therapy needed to achieve a cure is quite toxic and for those that do experience a disease recurrence, the prognosis is very dismal. Given this, there is a tremendous need for novel therapies for children with high-risk neuroblastoma and the molecular discoveries over recent years provide hope for developing new, less toxic, and potentially more efficacious treatments. Here I discuss many of the molecular aberrations identified thus far in neuroblastoma, as well as the agents in development to target these changes. The progress made in both the preclinical arena and in early phase drug development provide much promise for the future of precision medicine in neuroblastoma. Full article

Kawasaki disease (KD) is an inflammatory febrile illness of early childhood and the primary cause of acquired heart disease during childhood. Coronary artery aneurysms (CAA) are a serious complication of KD, leading to ischemic heart disease, myocardial infarction, and sudden cardiac death. Timely diagnosis in the first ten days of fever is crucial to reduce the risk of coronary artery complications. Nitrogen-terminal B-type natriuretic peptide (NT-proBNP), originally used for the management of adults with heart disease, was shown to be useful in the diagnosis and management of patients with KD. NT-proBNP is released by cardiomyocytes in response to mechanical factors such as the dilation of cardiac chambers, and to pro-inflammatory cytokines. The utility of NT-proBNP as a biological marker in KD is based on the universal myocardial inflammatory component early in the course of the disease. Patients with KD have higher NT-proBNP at the time of diagnosis than febrile controls, with a pooled sensitivity of 89% (95% confidence interval 78–95), and a specificity of 72% (95% confidence interval 58–82). The positive likelihood ratio is 3.2:1 (95% confidence interval 2.1–4.8). Moreover, patients with resistance to intravenous immunoglobulin treatment and CAA were found to have higher levels of NT-proBNP, suggesting a prognostic role. Nevertheless, the non-specificity of NT-proBNP to KD limits its use as a stand-alone test. In this light, a tentative associative retrospective diagnostic algorithm was highly reliable for including all cases at risk of CAA, which warrants further prospective studies for a better diagnostic index of suspicion and risk stratification of patients. Full article

Background: One of the promising strategies for increasing physical activity (PA) at school is to integrate it with academic learning. The purposes of this study were: (a) to examine differences in objectively measured PA levels between integrated PA with mathematics and traditional lessons, and (b) to evaluate the PA levels of different integrated PAs. Methods: Seventy-seven 4th grade students (41 males) were included in an intervention (Move for Thought program: M4T) group (n = 46) that utilized PA integrated with mathematics or a control group (n = 31). Accelerometer data from each student were collected during five complete school days. M4T and control classroom sessions were identified using teachers’ logs. Accelerometer data were extracted, processed separately, and aggregated into a single data set. Minutes and percent time at different PA intensities were obtained using accelerometer minute-by-minute predicted METs. Results: One-way ANOVAs on PA levels showed a significant group effect (F = 5.33, p < 0.05) on moderate-to-vigorous PA (MVPA) in favor of the M4T group, but not on sedentary and light PA. The most active integrated PA provided 10.88 min of MVPA (SD = 11.87; 21.38 ± 24.38%) in a 50 min class period. Conclusion: Integrating PA with mathematics in the classroom can contribute to increasing MVPA levels in children. Full article

Hypotonic solutions have been used in pediatrics for maintenance of intravenous (IV) hydration. However, recent randomized control trials and cohort studies have raised significant concerns for association with hospital-acquired hyponatremia (HAH). The study aimed to assess whether the use of hypotonic parenteral solutions (PS) compared with isotonic PS is associated with increased HAH risk in children with common pediatric conditions. Retrospective chart review of 472 patients aged 2 months to 18 years who received either isotonic or hypotonic PS as maintenance fluids. Administration of hypotonic PS was associated with a four-fold increase in risk of developing HAH in the univariate analysis, (unadjusted odds ratio (OR) = 3.99; 95% confidence interval (CI): 1.36–11.69, p = 0.01). Hypotonic PS were associated with HAH (p = 0.04) when adjusted for the level of admission serum CO₂. There was a mean decrease of serum sodium of 0.53 mEq/L in the hypotonic group compared to the mean increase of 4.88 mEq/L in the isotonic group. These data suggest that hypotonic PS are associated with HAH in children admitted for common pediatric conditions. Isotonic PS should be considered as a safer choice for maintenance fluid hydration. Full article

This study investigated whether children engaged in more physical activity (PA) on school days that included Forest School (FS) sessions than a regular school day or a school day with a Physical Education (PE) lesson. How FS sessions influenced children’s general levels of PA and wellbeing was also explored across gender. A mixed-methods study followed a sample of 59 child participants aged 7 to 9 years old, from four primary schools, whilst taking part in twelve weekly FS sessions. Measures included the PA Questionnaire for Older Children and accelerometry data together with an individual Write and Draw task to inform focus groups. Children had significantly greater levels of light PA on a FS day and a PE school day compared to a regular school day and children reported feeling both happier and relaxed as a consequence of the intervention. From the qualitative data, boys and girls reported different likes of the FS interventions, whereas their dislikes of FS were comparable. Findings from this research provide evidence for such outdoor, nature-based learning within the school curriculum contributing to daily PA in children. Full article

Background: The objective of this paper is to derive a wrist-placed cut-point threshold for distinguishing sedentary behaviors from light-intensity walking using the ActiGraph GT3X+ in children. Methods: This study employed a cross-sectional study design, typically used in measurement-related studies. A sample of 167 children, ages 5–11 years (mean ± SD: 8.0 ± 1.8 years), performed up to eight seated sedentary activities while wearing accelerometers on both wrists. Activities included: reading books, sorting cards, cutting and pasting, playing board games, eating snacks, playing with tablets, watching TV, and writing. Direct observation verified sedentary behavior from light activity. Receiver operator characteristic (ROC) analyses were used to determine optimal cut-point thresholds. Quantile regression models estimated differences between dominant and non-dominant placement. Results: The optimal cut-point threshold for the non-dominant wrist was 203 counts/5 s with sensitivity, specificity, and area under the curve (AUC) of 71.56, 70.83, and 0.72, respectively. A 10-fold cross-validation revealed an average AUC of 0.70. Statistically significant (p ≤ 0.05) differences in median counts ranging from 7 to 46 counts/5 s were found between dominant and non-dominant placement in five out of eight sedentary activities, with the dominant wrist eliciting higher counts/5 s. Conclusion: Results from this study support the recommendation to place accelerometers on the non-dominant wrist to minimize “noise” during seated sedentary behaviors. Full article

For decades, parenteral nutrition (PN) has been a successful method for intravenous delivery of nutrition and remains an essential therapy for individuals with intolerance of enteral feedings or impaired gut function. Although the benefits of PN are evident, its use does not come without a significant risk of complications. For instance, parenteral nutrition-associated liver disease (PNALD)—a well-described cholestatic liver injury—and atrophic changes in the gut have both been described in patients receiving PN. Although several mechanisms for these changes have been postulated, data have revealed that the introduction of enteral nutrition may mitigate this injury. This observation has led to the hypothesis that gut-derived signals, originating in response to the presence of luminal contents, may contribute to a decrease in damage to the liver and gut. This review seeks to present the current knowledge regarding the modulation of what is known as the “gut–liver axis” and the gut-derived signals which play a role in PN-associated injury. Full article

Despite the known benefits of engaging in daily moderate to vigorous physical activity (MVPA), only 22% of children in England are meeting the recommended guidelines. School break times have been advocated as a key part of children’s daily routines in which their MVPA can be increased. The main aim of this study was to evaluate the effect of installing a walking-track on children’s MVPA during school break times. A mixed method design was employed which allowed for the quantitative measurement of children’s PA at three time points (baseline, mid-intervention (1–5 weeks) and follow-up (6–9 weeks)), using pedometers (n = 81, 5–9 years) and systematic observation (n = 23, 7–9 years). A semi-structured interview (n = 1) was also conducted at 10 weeks’ follow-up. The installation of the walking-track was grounded in a unique set of theoretical constructs to aid the behaviour change of the teachers. Short term positive increases in girls’ and boys’ MVPA and longer term increases in boys’ vigorous PA (VPA) were found. Qualitative data highlighted that boys dominated the walking-track and the inconsistent behaviour of school staff negatively impacted upon children’s MVPA. A set of principles to guide the installment of walking-tracks in school playgrounds are recommended. Full article