Children, Volume 11, Issue 7 (July 2024) – 21 articles

Background: Perilipin 2 (PLIN2) is a protein that contributes to the formation and stability of lipid droplets. It has been associated with the development of several diseases, particularly related to glucose and lipid metabolism. In infants of diabetic mother (IDM), fetal hyperinsulinaemia leads to increased adipose tissue and macrosomia. The aim of this study was to investigate the relationship between PLIN2 levels and anthropometric measurements in the IDM and to investigate the relationship between PLIN2 levels and IGF-1, IGF-2 and leptin levels. Methods: The study group consisted of IDMs, while the control group consisted of infants born to non-diabetic mother, matched for gestational week and gender. Cord blood samples were collected from all patients to determine PLIN2, IGF-1, IGF-2 and leptin levels. Anthropometric measurements were taken for all patients at birth. Results: There were no differences between the groups in birth weight, birth length, head circumference and body mass index (BMI), but middle arm circumference, triceps, biceps, subscapular and suprailiac skinfold thickness were significantly higher in the IDM. While PLIN2, IGF-1, IGF-2 and leptin levels were similar between groups, there was a strong correlation between PLIN2 levels and IGF-2 and leptin levels. Conclusions: Even if IDMs were not macrosomic, the presence of high subcutaneous adipose tissue was not associated with PLIN2. Full article

Background: while most gut microbiota research has focused on term infants, the health outcomes of preterm infants are equally important. Very-low-birth-weight (VLBW) or extremely-low-birth-weight (ELBW) preterm infants have a unique gut microbiota structure, and probiotics have been reported to somewhat accelerate the maturation of the gut microbiota and reduce intestinal inflammation in very-low preterm infants, thereby improving their long-term outcomes. The aim of this study was to investigate the structure of gut microbiota in ELBW neonates to facilitate the early identification of different types of low-birth-weight (LBW) preterm infants. Methods: a total of 98 fecal samples from 39 low-birth-weight preterm infants were included in this study. Three groups were categorized according to different birth weights: ELBW (n = 39), VLBW (n = 39), and LBW (n = 20). The gut microbiota structure of neonates was obtained by 16S rRNA gene sequencing, and microbiome analysis was conducted. The community state type (CST) of the microbiota was predicted, and correlation analysis was conducted with clinical indicators. Differences in the gut microbiota composition among ELBW, VLBW, and LBW were compared. The value of gut microbiota composition in the diagnosis of extremely low birth weight was assessed via a random forest-machine learning approach. Results: we briefly analyzed the structure of the gut microbiota of preterm infants with low birth weight and found that the ELBW, VLBW, and LBW groups exhibited gut microbiota with heterogeneous compositions. Low-birth-weight preterm infants showed five CSTs dominated by Enterococcus, Staphylococcus, Klebsiella, Streptococcus, Pseudescherichia, and Acinetobacter. The birth weight and clinical indicators related to prematurity were associated with the CST. We found the composition of the gut microbiota was specific to the different types of low-birth-weight premature infants, namely, ELBW, VLBW, and LBW. The ELBW group exhibited significantly more of the potentially harmful intestinal bacteria Acinetobacter relative to the VLBW and LBW groups, as well as a significantly lower abundance of the intestinal probiotic Bifidobacterium. Based on the gut microbiota’s composition and its correlation with low weight, we constructed random forest model classifiers to distinguish ELBW and VLBW/LBW infants. The area under the curve of the classifiers constructed with Enterococcus, Klebsiella, and Acinetobacter was found to reach 0.836 by machine learning evaluation, suggesting that gut microbiota composition may be a potential biomarker for ELBW preterm infants. Conclusions: the gut bacteria of preterm infants showed a CST with Enterococcus, Klebsiella, and Acinetobacter as the dominant genera. ELBW preterm infants exhibit an increase in the abundance of potentially harmful bacteria in the gut and a decrease in beneficial bacteria. These potentially harmful bacteria may be potential biomarkers for ELBW preterm infants. Full article

Uveitis is an inflammatory disease that can lead to severe complications, including vision loss. The pediatric population is particularly at risk of developing complications, as uveitis in this age group often has idiopathic origins or is associated with systemic diseases that follow a severe course. This, coupled with unfavorable treatment outcomes, continues to be a challenge in pediatric ophthalmology. The cornerstone of uveitis treatment involves a therapeutic strategy that depends on the etiology, severity, and localization of the inflammation, as well as the patient’s response to treatment and the presence of ocular complications. Patients who do not receive timely treatment face a significantly increased risk of experiencing a severe disease course. Understanding potential therapeutic options and their side effects is crucial in managing children with uveitis. Equally important is the continuous monitoring of the child’s condition throughout the treatment process, due to the chronic and recurrent nature of uveitis in this demographic. The authors conducted a review of the current literature from 2018 to 2023 on the management and introduction of new therapeutic approaches for children with uveitis. Full article

Background: Despite the limited understanding of its precise mechanism of action, sacral nerve stimulation (SNS) has proven to be helpful for pediatric patients with constipation, particularly those with fecal incontinence. It is unclear whether the outcome of SNS is impacted by normal or abnormal colonic motility. Our study aimed to determine whether colonic manometry results had an impact on the outcome of SNS as a treatment in pediatric patients with refractory idiopathic constipation. Methods: Electronic medical records of patients with idiopathic constipation who underwent colonic manometry and SNS placement at our center over 6 years were reviewed. A comparison of post-SNS outcomes was performed between patients with normal and abnormal colonic manometry studies. Results: Twenty patients [12 (60%) females, median age of 10.2 years] met inclusion criteria, with fecal incontinence in 12 (60%) and abnormal colonic manometry in 6 (30%). Significantly more patients had an improvement in fecal incontinence following SNS placement (p = 0.045). There were no significant differences in post-SNS constipation outcome measures between patients with normal versus abnormal colonic manometry. Conclusions: Colonic manometry did not help with patient selection for those being considered for SNS therapy. Our findings do not support performing colonic manometry as a screening prior to SNS placement. Full article

The 22q11.2 deletion syndrome (DS) can have a significant impact on functionality. The purpose was to describe 22q11.2DS children with functioning from a biopsychosocial perspective, focusing on the impact of children’s health condition from domains of the International Classification of Functioning, Disability, and Health (ICF). Methods: A descriptive, cross-sectional case series study with seven 22q11.2DS children. A questionnaire with an ICF checklist for 22q11.2DS was completed using a structured interview. The Wechsler Abbreviated Scale of Intelligence (WASI) was used to determine the Intelligence Quotient (IQ). Results: Seven participants from 7 to 12 years old, presented some level of IQ impairment. It was observed that 22q11.2DS children experience significant intellectual, cognitive, and speech impairments across ICF Body Function domains. Impairments related to nose and pharynx were found in only one patient. The most relevant categories considered limitations in the Activity and Participation components pertained to producing nonverbal messages, communication, handling stress, and social interaction. Family, health professionals, and acquaintances were perceived as facilitators in the component Environmental Factors. Conclusion: The sample has its functioning affected by aspects that go beyond impairments in body structure and function. The organization of information from the perspective of the ICF is a different approach that helps clinical reasoning. Full article

Previous research has shown that moral emotions interact with self-control and unstructured socializing in explaining rule-breaking behavior. High levels of moral emotions appear to weaken the effects of both self-control and unstructured socializing, in explaining rule-breaking behavior. The current study examined whether these interactions also affect rule-breaking behavior that is explicitly committed with friends. In addition, three operationalizations of moral emotions were distinguished. Data were collected from N = 169 adolescents (54% female; mean = 14.95 years; SD = 1.7) using a self-report questionnaire battery. Results indicate that high levels of anticipated emotions in moral conflicts (AEMC) attenuate the effect of low self-control on one’s own rule-breaking behavior. In contrast, high levels of both guilt- and shame-proneness enhanced the effect of unstructured socializing on one’s own and rule-breaking with friends. The limitations of the study, ideas for future research, and practical implications are also discussed. Full article

Background: Cerebrovascular autoregulation (CAR) is often impaired in preterm infants but requires invasive mean arterial blood pressure (MABP) measurements for continuous assessment. We aimed to assess whether using heart rate (HR) results in different CAR assessment compared with using MABP. Methods: We compared CAR (moving window correlation-coefficient with cerebral oxygenation saturation (r_cSO₂)), and percentage of time with impaired CAR (%timeCARi) calculated by either HR (TOHRx, tissue oxygenation heart rate reactivity index) or MABP (COx, cerebral oximetry index) during the first 72 h after birth, and its association with short-term cerebral injury. Results: We included 32 infants, median gestational age of 25 + 5/7 weeks (interquartile range 24 + 6/7–27 + 5/7). COx and TOHRx correlation coefficients (cc) were significantly different in the first two days after birth (individual means ranging from 0.02 to 0.07 and −0.05 to 0.01). %TimeCARi using MABP (cc cut-off 0.3), was higher on day 1 (26.1% vs. 17.7%) and day 3 (23.4% vs. 16.9%) compared with HR (cc cutoff –0.3). During 65.7–69.6% of the time, both methods indicated impaired CAR simultaneously. The aforementioned calculations were not associated with early cerebral injury. Conclusions: In conclusion, HR and MABP do not seem interchangeable when assessing CAR in preterm infants. Full article

Universal health coverage has been proposed as a strategy to improve health in low- and middle-income countries, but this depends on a good provision of health services. Under-5 mortality (U5M) reflects the quality of health services, and its reduction has been a milestone in modern society, reducing global mortality rates by more than two-thirds between 1990 and 2020. However, despite these impressive achievements, they are still insufficient, and most deaths in children under 5 can be prevented with the provision of timely and high-quality health services. The aim of this paper is to conduct a literature review on amenable (treatable) mortality in children under 5. This indicator is based on the concept that deaths from certain causes should not occur in the presence of timely and effective medical care. A systematic and exhaustive review of available literature on amenable mortality in children under 5 was conducted using MEDLINE/PubMed, Cochrane CENTRAL, OVID medline, Scielo, Epistemonikos, ScienceDirect, and Google Scholar in both English and Spanish. Both primary sources, such as scientific articles, and secondary sources, such as bibliographic indices, websites, and databases, were used. Results: The main cause of amenable mortality in children under 5 was respiratory disease, and the highest proportion of deaths occurred in the perinatal period. Approximately 65% of avoidable deaths in children under 5 were due to amenable mortality, that is, due to insufficient quality in the provision of health services. Most deaths in all countries and around the world are preventable, primarily through effective and timely access to healthcare (amenable mortality) and the management of public health programs focused on mothers and children (preventable mortality). Full article

Arachnoid granulations (AGs) are generally benign structures within the subarachnoid space that extend into the dural sinuses and calvarial bone. They can present in a variety of sizes but are termed ‘giant’ arachnoid granulations (GAGs) when they are larger than 1 cm in diameter or take up a significant portion of the dural sinus’ lumen. Vermiform giant arachnoid granulations are a specific type of GAG that are known for their worm-like appearance. Specifically, these vermiform GAGs can be challenging to diagnose as they can mimic other pathologies like dural sinus thrombosis, sinus cavernomas, or brain tumors. In this case series, we present two cases of vermiform giant arachnoid granulations, discuss their imaging characteristics and highlight the diagnostic challenges to improve identification and prevent misdiagnoses. Full article

Artificial intelligence has been applied to medical diagnosis and decision-making but it has not been used for classification of Class III malocclusions in children. Objective: This study aims to propose an innovative machine learning (ML)-based diagnostic model for automatically classifies dental, skeletal and functional Class III malocclusions. Methods: The collected data related to 46 cephalometric feature measurements from 4–14-year-old children (n = 666). The data set was divided into a training set and a test set in a 7:3 ratio. Initially, we employed the Recursive Feature Elimination (RFE) algorithm to filter the 46 input parameters, selecting 14 significant features. Subsequently, we constructed 10 ML models and trained these models using the 14 significant features from the training set through ten-fold cross-validation, and evaluated the models’ average accuracy in test set. Finally, we conducted an interpretability analysis of the optimal model using the ML model interpretability tool SHapley Additive exPlanations (SHAP). Results: The top five models ranked by their area under the curve (AUC) values were: GPR (0.879), RBF SVM (0.876), QDA (0.876), Linear SVM (0.875) and L2 logistic (0.869). The DeLong test showed no statistical difference between GPR and the other models (p > 0.05). Therefore GPR was selected as the optimal model. The SHAP feature importance plot revealed that he top five features were SN-GoMe (the ratio of the length of the anterior skull base SN to that of the mandibular base GoMe), U1-NA (maxillary incisor angulation to NA plane), Overjet (the distance between two lines perpendicular to the functional occlusal plane from U1 and L), ANB (the difference between angles SNA and SNB), and AB-NPo (the angle between the AB and N-Pog line). Conclusions: Our findings suggest that ML models based on cephalometric data could effectively assist dentists to classify dental, functional and skeletal Class III malocclusions in children. In addition, features such as SN_GoMe, U1_NA and Overjet can as important indicators for predicting the severity of Class III malocclusions. Full article

Background: Child footwear, both in pathologies and in normal situations, can affect the foot in various ways depending on its characteristics. Below, some features of child footwear are described, and how they can influence the foot, including suitable size, shape and design, flexibility, and transpirable material; inadequate footwear includes situations with flat foot, equine foot, and hammer toes. It is important to highlight that each child is unique and may have different footwear needs. In case of specific pathologies or concerns, it is recommended to consult a specialist in podology or foot medicine for personalized assessment and recommendations. Methods: The present systematic review was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Children’s footwear must adapt to all stages of children’s growth, starting from when they begin to walk, to promote the correct evolution of their musculoskeletal system. For up to six months, they do not need to wear shoes; socks and similar clothing are enough to warm your feet like a second skin. The flexibility of respectful footwear is essential between six months and three or four years. From that age onwards, the soles can be somewhat thicker, and the buttress can have a certain firmness, but the shoes should remain flexible. Conclusions: Eco-friendly footwear, which typically comes from small businesses and factories, is sometimes described as “ergonomic footwear”. However, there is some reluctance towards this term. When choosing this type of footwear for children, it is important to not just look at the label; rather, one should verify that it meets all the necessary characteristics to be considered respectful. Full article

Introduction: Subtalar Arthroereisis (STA) is a surgical intervention for pediatric flexible flatfoot (PFF), primarily targeting hindfoot alignment by limiting excessive subtalar eversion. However, its effects on forefoot parameters remain underexplored. This study aims to investigate radiological changes following STA in pediatric patients. Materials and Methods: A retrospective analysis was conducted on consecutive patients treated with STA for PFF. First ray-related angles, including the Hallux Valgus Angle (HVA) and the Intermetatarsal Angle (IMA), alongside hindfoot radiological parameters such as the Meary, Calcaneal Pitch, and Costa Bartani angles, were assessed. Subgroup analysis by gender was performed, and correlations between demographic and preoperative radiological parameters were examined. Results: Forty-one patients (81 feet) with an average age of 11.6 years were included, with a mean follow-up duration of 6.4 months. No significant differences were observed in first ray-related angles pre-and postoperatively, with the mean IMA changing from 7.97° to 7.18° and the mean HV angles changing from 9.51° to 8.66°. Noteworthy improvements were seen in flat foot angles, including the Meary, Calcaneal Pitch, and Costa Bartani angles, postoperatively. The age subgroup analysis revealed similar trends in IMA and HVA changes between Group A (who underwent surgery before peak growth) and Group B (who underwent surgery after peak growth). Higher preoperative angles tended to improve, while lower preoperative IMAs and HVAs tended to worsen postoperatively, all remaining within normal ranges. Conclusion: STA showed positive radiological outcomes for PFF treatment, while negligible changes in first ray-related angles were observed. The age subgroup analysis indicated similar trends regardless of operation timing. Higher preoperative angles tended to improve, while lower preoperative angles tended to worsen postoperatively, despite all falling within non-pathological ranges. Further research is warranted to confirm this correlation. Full article

Background: Specific learning disorder (SLD) is a neurodevelopmental condition characterised by significant academic difficulties despite normal intelligence and adequate education. The difficulties with reading, writing, and arithmetic may manifest independently or concurrently at different ages. Early symptoms may appear in preschool, including delays in social skills, motor skills, and language development. This study aimed to assess the prevalence of preschool children at risk for SLD and related psychiatric disorders. Method: Data were collected from 515 preschool children in Edirne City, Turkey, using a screening scale for early symptoms of SLD. Socio-demographic information was obtained, and children at risk were invited for a psychiatric evaluation. Results: The mean age of the participants was 72.5 ± 5.6 months. It was determined that 5.7% of the preschool children who participated in the questionnaire were at risk of SLD according to the screening scale scores. Factors such as a father’s low education, the mother smoking during pregnancy, a longer stay in the neonatal intensive care unit, longer screen time, and consanguinity between parents were associated with an increased risk of SLD. Conclusion: This study emphasises the importance of early identification and intervention for SLD and the need to consider associated psychiatric comorbidities. Identifying the risk factors in preschool children may facilitate timely intervention and prevent academic and social difficulties in later years. Full article

Background: Poor quality of sleep is a widespread issue in modern society, and even children are being diagnosed with sleep disorders nowadays. Sleep disruption in children can lead to poor mental health in the long term. The present study aimed to evaluate the association between sleep disorders and subsequent depression in children and adolescents. Methods: This retrospective cohort study used electronic medical records from the IQVIA^TM Disease Analyzer database. It included children and adolescents aged 6–16 with an initial diagnosis of a sleep disorder and age- and gender-matched patients without sleep disorders treated by one of 274 office-based pediatricians in Germany between January 2010 and December 2022. The five-year cumulative incidence of depression in the cohorts with and without sleep disorders was studied with Kaplan–Meier curves using the log-rank test. Multivariable Cox regression analyses were used to assess the association between sleep disorders and depression. Results: The present study included 10,466 children and adolescents with and 52,330 without sleep disorder diagnosis (mean age 10 ± 3 years, 48% female). Within five years after the index date, 5% of sleep disorder patients and 2% of the matched non-sleep disorder cohort had been diagnosed with depression. A strong and significant association was observed between sleep disorders and subsequent depression (HR: 2.34; 95% CI: 2.09–2.63). This association was stronger in adolescents (HR: 3.78; 95% CI: 3.13–4.56) than in children. Upon the exclusion of depression diagnoses in the first year after the index date, the association between sleep disorders and depression remained strong and significant (HR: 1.92; 95% CI: 1.68–2.19). Conclusions: This study indicates a strong and significant association between sleep disorders and depression. Full article

Attention deficit hyperactivity disorder (ADHD) is among the most prevalent disorders in children and is frequently linked with motor difficulties that can impact both daily motor tasks and overall developmental trajectories. The objective of this study was to analyse the association between gross motor skills and ADHD symptoms. Using a cross-sectional research design, data were collected from a sample of primary school children (N = 2677; mean age = 8.58 years, SD = 1.49 years). The Gross Motor Development-3 Test (TGMD-3) was employed to assess participants’ gross motor skills, whereas the ADHD Rating Scale (SDAI), completed by teachers, evaluated ADHD symptoms through two subscales: inattention and impulsivity/hyperactivity. The results revealed an association between motor development and ADHD symptoms, with greater proficiency in gross motor skills correlating with lower symptoms reported on the SDAI. Logistic regression analyses indicated that the TGMD-3 was significantly associated with the risk of ADHD in matched samples of at-risk children and controls. The evaluation of gross motor development proves to be a useful tool for monitoring global development, paying attention to any critical issues, particularly in relation to the variables of inattention and hyperactivity. Full article

Abstract: Understanding how children comprehend text by forming links between sentences has been the focus of research for decades. Such research has consistently shown that children use anaphors and resolve ambiguities in a different manner than adults. The present study examined a less-studied anaphoric reference that arises when two numerically quantified expressions (e.g., “three cats… two cats…”) are used in the text. Focusing on 249 six- to eight-year-old children and 50 adults for comparison, the study employed a picture selection task across six experiments to assess interpretative preferences in ambiguous and unambiguous discourses containing numerically quantified expressions. The findings indicate a pronounced difference in interpretative strategies: unlike adults, who predominantly adopted an anaphoric subset reading, children showed a consistent preference for the non-anaphoric reading, even in contexts explicitly disambiguated towards this interpretation. This preference persisted across various experimental manipulations, highlighting challenges in text integration and comprehension among children. Contributing to the developmental trajectory of language comprehension, this study underscores the complexity of cognitive development and linguistic interpretation, revealing significant developmental differences in processing numerically quantified expressions and anaphoric references within discourse. Full article

Macrophage activation syndrome (MAS) is potentially fatal; so, early diagnosis and timely treatment are essential. However, detecting MAS is sometimes challenging because its principal features can be observed in other pediatric diseases that cause severe inflammation. Cytokine storm due to immune dysregulation represents the clinical and laboratory features of MAS that are included in the diagnostic criteria. Most cases of MAS occur as an underlying condition worsens and progresses. Therefore, a patient with autoimmune or autoinflammatory disease who shows unexplained clinical deterioration despite appropriate management should be considered at high risk for MAS (i.e., occult MAS). The basic principles of treatment are control of triggering factors, supportive care, and relief of hyperinflammation. Systemic steroids and cyclosporine A are frequently used as a first-line treatment. For the treatment of refractory MAS, cytokine-specific biologic agents such as anakinra have recently become preferred over traditional immunosuppressive agents such as etoposide. MAS might be underrecognized in pediatric patients with infectious and inflammatory diseases due to its diverse clinical presentations. Clinical suspicion of MAS is of the utmost importance for early recognition of the disease. Full article

The role and potential impact of digital screen technology in the lives of children is heavily debated. Current evidence is limited by the weakness of measures typically used to characterise screen use, predominantly proxy- or self-reports with known inaccuracy and bias. However, robust and detailed evidence is needed to provide practical trustworthy guidance to families and professionals working with families. The purpose of this paper is to support researchers to select measurement method(s) that will provide robust and detailed evidence. The paper outlines the challenges in measuring contemporary screen use by children, using a child–technology interaction model to organise considerations. A range of different methods used to measure digital screen technology use in children and adolescents (i.e., questionnaires, diaries, electronically prompted sampling, direct observation, fixed room cameras, wearable/portable cameras, audio recorders, screen-device onboard logging, remote digital trace logging and proximity logging) are described along with examples of their use and constructs typically measured as well as a summary of the advantages and disadvantages of each method. A checklist and worked examples are provided to support researchers determining the best methods or combination of methods for a research project. Full article

Macrodactyly is a rare congenital limb difference manifesting as an overgrowth of one or more fingers or toes. The pathological process affects all tissues of the ray in the hand or foot. The enlargement can significantly alter the limb’s appearance and impair its function. The role of a pediatrician is to distinguish isolated macrodactyly from syndromic conditions (including PIK3CA-Related Overgrowth Spectrum) or mimicking conditions to enable early interdisciplinary consultation and treatment planning. The psychological stigma associated with this often disfiguring condition necessitates support for patients and their family. We present a practical guide for physicians who might be the first to raise suspicion of macrodactyly and initiate further diagnostics to achieve adequate treatment and support for children and caregivers. Full article

Magnetic resonance imaging is currently used in the neonatal setting for assessing features of the neonatal brain. However, its utilization is constrained by logistic, technical, or clinical challenges. Brain elastography is a new research technique which enhances the diagnostic capability of traditional imaging, and can be paired with both ultrasonography and magnetic resonance imaging. In particular, brain elastography adds objective and quantitative information to traditional imaging by detecting differences in tissue elasticity/stiffness, which may represent a surrogate marker of the physiologic and pathologic features of the neonatal brain. To date, very limited experience exists about the use of brain elastography specifically in the neonatal setting. The aim of the present review was to describe the most recent information about the feasibility and diagnostic accuracy of brain ultrasound elastography (USE) in neonates, and to provide information about the possible future applications and perspectives of brain elastography. Full article

Moral distress is a complex phenomenon whereby a person feels tension, constraint, or conflict with an action or circumstance because it goes against their individual or the perceived collective (e.g., community, organizational, or professional association’s) moral stance. In pediatric healthcare settings, managing and mitigating feelings of moral distress can be particularly difficult to navigate through because of the intricate dynamics between the pediatric patient, parent and/or legal guardians, and clinicians. The proactive integration of an experienced pediatric palliative care (PPC) team can be an appropriate step toward reducing clinicians feeling overwhelmed by various case-specific and team management issues that contribute to the development of moral distress among healthcare professionals. Based on our experiences in a free-standing, quaternary pediatric hospital, the involvement of PPC can help reframe the approach to challenging situations, enhance communication, and provide guidance to the care team, patients, and families. Moreover, PPC teams can benefit other multidisciplinary team members through education on respecting the plurality of values of diverse families and patients and consideration of ethical implications during morally challenging situations. Full article