Correlations between Sleep Features and Iron Status in Children with Neurodevelopmental Disorders: A Cross-Sectional Study.

A high prevalence of sleep disturbances has been reported in children with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID). The etiology of sleep disorders in these children is heterogeneous and, recently, iron deficiency has received increasing attention. This study aims to investigate sleep features in children with NDDs and to explore a possible correlation between serum iron status biomarkers and qualitative features of sleep. We included 4- to 12-year-old children with a diagnosis of ASD, ADHD, or ID and assessed their sleep features through the children's sleep habits questionnaire (CSHQ). Venous blood samples were collected to investigate ferritin, transferrin, and iron levels. The mean CSHQ total score exceeds the cut-off in all groups of children. In the ASD group, the Parasomnias subscale negatively correlated with serum ferritin levels (Rho = 0.354; p = 0.029). Our findings may suggest the existence of an association between iron status, sleep quality, and neurodevelopmental processes. In clinical practice, sleep assessment should be included in the routine assessment for patients with NDDs. Furthermore, a routine assessment of iron status biomarkers should be recommended for children with NDDs who have sleep disturbances.

Cardiac autonomic control in Rett syndrome: Insights from heart rate variability analysis.

Rett syndrome (RTT) is a rare and severe neurological disorder mainly affecting females, usually linked to methyl-CpG-binding protein 2 (MECP2) gene mutations. Manifestations of RTT typically include loss of purposeful hand skills, gait and motor abnormalities, loss of spoken language, stereotypic hand movements, epilepsy, and autonomic dysfunction. Patients with RTT have a higher incidence of sudden death than the general population. Literature data indicate an uncoupling between measures of breathing and heart rate control that could offer insight into the mechanisms that lead to greater vulnerability to sudden death. Understanding the neural mechanisms of autonomic dysfunction and its correlation with sudden death is essential for patient care. Experimental evidence for increased sympathetic or reduced vagal modulation to the heart has spurred efforts to develop quantitative markers of cardiac autonomic profile. Heart rate variability (HRV) has emerged as a valuable non-invasive test to estimate the modulation of sympathetic and parasympathetic branches of the autonomic nervous system (ANS) to the heart. This review aims to provide an overview of the current knowledge on autonomic dysfunction and, in particular, to assess whether HRV parameters can help unravel patterns of cardiac autonomic dysregulation in patients with RTT. Literature data show reduced global HRV (total spectral power and R-R mean) and a shifted sympatho-vagal balance toward sympathetic predominance and vagal withdrawal in patients with RTT compared to controls. In addition, correlations between HRV and genotype and phenotype features or neurochemical changes were investigated. The data reported in this review suggest an important impairment in sympatho-vagal balance, supporting possible future research scenarios, targeting ANS.

Peripheral Iron Levels in Autism Spectrum Disorders vs. Other Neurodevelopmental Disorders: Preliminary Data.

Autism Spectrum Disorder (ASD) is characterized by deficits in social skills and specific behaviors and interests. Among other environmental factors, iron may play a role in the development of ASD. The aim of this study is to compare the iron status of children with ASD with that of children affected by neurodevelopmental disorders other than ASD (OND). A total of 167 patients were enrolled, including 93 children with ASD and 74 children with OND. In the two groups, we determined ferritin, iron, transferrin, hemoglobin, HCT, and MCV in the serum. We found a significant difference in serum ferritin and MCV levels between the two groups (p < 0.05), with lower ferritin and higher MCV values in the ASD group. There was no significant association with the other variables. Our results may support the hypothesis of altered iron status in ASD, justifying more frequent examinations of blood iron parameters in these children.

B and T Immunoregulation: A New Insight of B Regulatory Lymphocytes in Autism Spectrum Disorder.

Introduction: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by a complex pathogenesis, by impairment social communication and interaction, and may also manifest repetitive patterns of behavior. Many studies have recognized an alteration of the immune response as a major etiological component in ASDs. Despite this, it is still unclear the variation of the function of the immune response. Aim: Our aim is to investigate the levels of immunological markers in peripheral blood of children with ASD such as: regulatory B and T cells, memory B and natural killer (NK) cells. Materials and Methods: We assessed various subsets of immune cells in peripheral blood (regulatory B and T cells, B-cell memory and natural killer cells) by multi-parametric flow cytometric analysis in 26 ASD children compared to 16 healthy controls (HCs) who matched age and gender. Results: No significant difference was observed between B-cell memory and NK cells in ASDs and HCs. Instead, regulatory B cells and T cells were decreased (p < 0.05) in ASD subjects when compared to HCs. Discussion: Regulatory B and T cells have a strategic role in maintaining the immune homeostasis. Their functions have been associated with the development of multiple pathologies especially in autoimmune diseases. According to our study, the immunological imbalance of regulatory B and T cells may play a pivotal role in the evolution of the disease, as immune deficiencies could be related to the severity of the ongoing disorder.

Subjective and Electroencephalographic Sleep Parameters in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review.

BACKGROUND: Sleep problems have commonly manifested in children and adolescents with autism spectrum disorder (ASD) with a complex and multifactorial interaction between clinical and etiological components. These disorders are associated with functional impairment, and provoke significant physical and mental affliction. The purpose of this study is to update the existing literature about objective and subjective sleep parameters in children and adolescents with ASD, extrapolating information from polysomnography or sleep electroencephalography, and sleep related questionnaires. METHODS: We have conducted a systematic review of case-control studies on this topic, performing a web-based search on PubMed, Scopus and the Web of Science databases according to the Preferred Reporting items for Systematic Review and Meta-analyses (PRISMA) guidelines. RESULTS: Data collected from 20 survey result reports showed that children and adolescents with ASD experienced a higher rate of sleep abnormalities than in typically developing children. The macrostructural sleep parameters that were consistent with subjective parent reported measures unveil a greater percentage of nighttime signs of insomnia. Sleep microstructure patterns, in addition, pointed towards the bidirectional relationship between brain dysfunctions and sleep problems in children with ASD. CONCLUSIONS: Today's literature acknowledges that objective and subjective sleep difficulties are more often recognized in individuals with ASD, so clinicians should assess sleep quality in the ASD clinical population, taking into consideration the potential implications on treatment strategies. It would be worthwhile in future studies to examine how factors, such as age, cognitive level or ASD severity could be related to ASD sleep abnormalities. Future research should directly assess whether sleep alterations could represent a specific marker for atypical brain development in ASD.