Sleep After Concussion: A Scoping Review of Sensor Technologies.

Sleep disturbances following a concussion/mild traumatic brain injury are associated with longer recovery times and more comorbidities. Sensor technologies can directly monitor sleep-related physiology and provide objective sleep metrics. This scoping review determines how sensor technologies are currently used to monitor sleep following a concussion. We searched Ovid (Medline, Embase), Web of Science, CINAHL, Compendex Engineering Village, and PsycINFO from inception to June 20, 2022, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. Included studies objectively monitored sleep in participants with concussion. We screened 1081 articles and included 37 in the review. A total of 17 studies implemented polysomnography (PSG) months to years after injury for a median of two nights and provided a wide range of sleep metrics, including sleep-wake times, sleep stages, arousal indices, and periodic limb movements. Twenty-two studies used actigraphy days to weeks after injury for a median of 10 days and nights and provided information limited to sleep-wake times. Sleep stages were most reported in PSG studies, and sleep efficiency was most reported in actigraphy studies. For both technologies there was high variability in reported outcome measures. Sleep sensing technologies may be used to identify how sleep affects concussion recovery. However, high variability in sensor deployment methodologies makes cross-study comparisons difficult and highlights the need for standardization. Consensus on how sleep sensing technologies are used post-concussion may lead to clinical integration with subjective methods for improved sleep monitoring during the recovery period.

Melatonin use in managing insomnia in children with autism and other neurogenetic disorders - An assessment by the international pediatric sleep association (IPSA).

Though it is widely prescribed for improving sleep of children with autism and other neurogenetic disorders, there is a need for practical guidance to clinicians on the use of melatonin for managing insomnia in this population. Because data were either lacking or inconclusive, a task force was established by the International Pediatric Sleep Association (IPSA) to examine the literature based on clinical trials from 2012 onwards. A summary of evidence pertaining to melatonin's utility and potential side effects, practice-related caveats, and insights for use are published herewith.

An eHealth Program for Insomnia in Children With Neurodevelopmental Disorders (Better Nights, Better Days): Protocol for an Economic Evaluation of a Randomized Controlled Trial.

BACKGROUND: Children with neurodevelopmental disorders have a high risk of sleep disturbances, with insomnia being the most common sleep disorder (ie, chronic and frequent difficulties with going and staying asleep). Insomnia adversely affects the well-being of these children and their caregivers. Pediatric sleep experts recommend behavioral interventions as the first-line treatment option for children. Better Nights, Better Days for Children with Neurodevelopmental Disorders (BNBD-NDD) is a 5-session eHealth behavioral intervention delivered to parents to improve outcomes (eg, Pediatric Quality of Life Inventory [PedsQL]) for their children (ages 4-12 years) with insomnia and who have a diagnosis of mild to moderate attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, or fetal alcohol spectrum disorder. If cost-effective, BNBD-NDD can be a scalable intervention that provides value to an underserved population. OBJECTIVE: This protocol outlines an economic evaluation conducted alongside the BNBD-NDD randomized controlled trial (RCT) that aims to assess its costs, efficacy, and cost-effectiveness compared to usual care. METHODS: The BNBD-NDD RCT evaluates the impacts of the intervention on children's sleep and quality of life, as well as parents' daytime functioning and psychosocial health. Parent participants were randomized to the BNBD-NDD treatment or to usual care. The economic evaluation assesses outcomes at baseline and 8 months later, which include the PedsQL as the primary measure. Quality of life outcomes facilitate the comparison of competing interventions across different populations and medical conditions. Cost items include the BNBD-NDD intervention and parent-reported usage of private and publicly funded resources for their children's insomnia. The economic evaluation involves a reference case cost-effectiveness analysis to examine the incremental cost of BNBD-NDD per units gained in the PedsQL from the family payer perspective and a cost-consequence analysis from a societal perspective. These analyses will be conducted over an 8-month time horizon. RESULTS: Research funding was obtained from the Kids Brain Health Network in 2015. Ethics were approved by the IWK Health Research Ethics Board and the University of Calgary Conjoint Health Research Ethics Board in January 2019 and June 2022, respectively. The BNBD-NDD RCT data collection commenced in June 2019 and ended in April 2022. The RCT data are currently being analyzed, and data relevant to the economic analysis will be analyzed concurrently. CONCLUSIONS: To our knowledge, this will be the first economic evaluation of an eHealth intervention for insomnia in children with neurodevelopmental disorders. This evaluation's findings can inform users and stakeholders regarding the costs and benefits of BNBD-NDD. TRIAL REGISTRATION: ClinicalTrial.gov NCT02694003; https://clinicaltrials.gov/study/NCT02694003. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46735.

Hyperactivity in patients with narcolepsy and idiopathic hypersomnia: an exploratory study.

Introduction: Patients with either Idiopathic Hypersomnia or Narcolepsy demonstrate excessive daytime somnolence (EDS) with resultant inattention mimicking Attention Deficit Hyperactivity Disorder (ADHD). Patients with ADHD also often express sleep problems including EDS. Thus, patients with ADHD and patients with idiopathic hypersomnia or narcolepsy may share inattention and daytime drowsiness as common features. However, it is not known whether EDS patients with idiopathic hypersomnia or narcolepsy also have increased movement (hyperactivity) like ADHD patients, the determination of which is the purpose of this study. Methods: We studied 12 patients (7 Narcolepsy type 2 and 5 Idiopathic Hypersomnia) with EDS as shown by Multiple Sleep Latency Test which served as the gold standard for entry into the study. Twelve subjects without symptoms of EDS served as the control group. None of the participants had a previous history of ADHD. Each participant underwent a one-hour session laying at 45 degrees with surveys about the need to move and actigraphy as an objective measure of movement. Results: Sleep-disordered patients with EDS reported more symptoms of inattention and hyperactivity on the ADHD Self-Report Scale. At each of the time points patients with EDS had a clear trend to express the need to move more than controls on the Suggested Immobilization Test (SIT). For the total 60 minutes, a large effect size for the need to move during the SIT test was found between patients and controls (Cohen's d = 0.61, p=0.01). Patients with EDS did not express a need to move more to combat drowsiness than controls, nor did actigraphy show any difference in objective movement between patients and controls during the SIT. Conclusion: Patients with EDS express inattention and a need to move more than controls. However, hyperactivity was not verified by objective measurement, nor did the EDS patients express a need to move to combat drowsiness more than controls. Thus, a hypothesis to be further tested, is whether narcolepsy and idiopathic hypersomnia may be more a model of the inattentive form of ADHD rather than the combined or inattentive/hyperactive form of ADHD. Further studies are needed to explore the relationship between EDS and hyperactivity.

Social-ecological considerations informing a universal screening strategy for sleep health in the community.

"Poor sleep health" (PSH), defined as reduced amount of sleep and non-restorative sleep, affects cognitive, social and emotional development. Evidence suggests an association of sleep deprivation and mental health problems; however, there are no universal concepts allowing a first-tier screening of PSH at a community level. The focus of this narrative review is to highlight the cultural context of the current medicalized approach to PSH and to suggest social ecological strategies informing new and holistic community-based screening concepts. We present two conceptual screening frameworks; a "medical" and a merged "social emotional wellbeing framework" and combine them utilizing the concept of "ecologies." The first framework proposes the incorporation of "sleep" in the interpretation of "vigilance" and "inappropriate" labeled behaviors. In the first framework, we provide a logic model for screening the myriad of presentations and possible root causes of sleep disturbances as a tool to assess daytime behaviors in context with PSH. In the second framework, we provide evidence that informs screening for "social emotional wellbeing" in the context of predictive factors, perpetuating factors and predispositions through different cultural perspectives. The distinct goals of both frameworks are to overcome training-biased unidirectional thinking and a priori medicalization of challenging, disruptive and/or disobedient behaviors. The latter has been explicitly informed by the critical discourse on colonization and its consequences, spearheaded by First Nations. Our "transcultural, transdisciplinary and transdiagnostic screening framework" may serve as a starting point from which adaptations of medical models could be developed to suit the purposes of holistic screening, diagnosis, and treatment of complex childhood presentations in different cultural contexts.

Understanding patient characteristics and medication prescriptions in children with mental health and neurodevelopmental disorders referred to a sleep clinic-A quality improvement/quality assurance analysis.

Introduction: Motivated by challenges faced in outpatient sleep services for mental health and neurodevelopmental disorders (MHNDD) during the COVID-19 clinical shutdown, a pan-Canadian/international working group of clinicians and social scientists developed a concept for capturing challenging sleep and wake behaviours already at the referral stage in the community setting. Methods: In a quality improvement/quality assurance (QIQA) project, a visual logic model was the framework for identifying the multiple causes and possible interventions for sleep disturbances. Intake forms informed clinicians about situational experiences, goals/concerns, in addition to the questions from the Sleep Disturbances Scale for Children (SDSC), the ADHD Rating Scale-IV and medication history. Descriptive statistics were used to describe the sample. Results: 66% of the pilot study patients (n = 41) scored in the SDSC red domains (highest scoring) with highest sub-scores for insomnia (falling asleep 73%; staying asleep: 51%) and daytime somnolence (27%). A total of 90% of patients were taking at least one medication; 59% sleep initiation/sleep medications, 41% in combination with further non-stimulant medications, 9% with stimulants, 27% with antidepressants and 18% with antipsychotics. Polypharmacy was observed in 62% of all patients and in 73% of the ones medicated for sleep disturbances. Qualitative information supported individualisation of assessments. Conclusion: Our intake process enabled a comprehensive understanding of patients' sleep and wake profiles prior to assessment, at the referral stage. The high prevalence of insomnia in patients, combined with polypharmacy, requires special attention in the triaging process at the community level.

Behavioral sleep medicine-The need for harmonization of clinical best practice outcome measures in children and adolescents with intellectual or developmental disabilities and restless sleep.

In behavioral medicine, sleep disorders, insomnia in particular, may be considered comorbidities and precipitating factors to intellectual or developmental disabilities (IDD). Nevertheless, sleep alterations have often been neglected in favor of daytime features and symptoms, albeit simple behavioral nighttime observations may disclose hypermotor features that characterize restless sleep. The root of most hypermotor restlessness is linked to central iron deficiency. The latter is often exacerbated by vitamin D deficiency (VDD), which interferes with both dopaminergic and serotonergic mechanisms. In this way, an imbalance affecting daytime behavior and mood is created. Several sleep-related motor disorders such as bruxism, periodic and aperiodic leg movements, Restless Legs Syndrome (RLS), and Restless Sleep Disorder (RSD) are commonly seen in Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD). However, they are rarely diagnosed and often overlooked in affected children and adolescents. As a result, not only are these disorders not adequately addressed therapeutically, but their symptoms may be worsened by the side-effects of drugs used to contain disruptive daytime behavior, such as antipsychotics and antidepressants. In children with IDDs, obesity, inactivity and metabolic effects of antipsychotics often lead to Sleep Disordered Breathing (SDB), which is currently understood as an inflammatory state leading to "hyperactive" lethargy and further alterations of the hypoxic chain and vitamin D levels. Endorsing simple routine blood tests, including inflammatory markers such as C-reactive protein, ferritin, transferrin, and vitamin D levels, may favorably complement caregiver observations and ambulatory sleep recordings, leading to a sleep disorder diagnosis and consequent therapy. In fact, the treatment of SDB, RLS, and RSD has been copiously demonstrated to favorably impact vigilance, behavior, social competence, and academic skills in healthy and, to a greater extent, in IDD children. Thus, consulting and deliberating the root causes of functional and categorical diagnoses within a clinical framework may engender a more precise diagnosis and further benefit pediatric daytime and nighttime management of hyperactive behaviors.

Iron deficiency and common neurodevelopmental disorders-A scoping review.

BACKGROUND: A wealth of human and experimental studies document a causal and aggravating role of iron deficiency in neurodevelopmental disorders. While pre-, peri-, and early postnatal iron deficiency sets the stage for the risk of developing neurodevelopmental disorders, iron deficiency acquired at later ages aggravates pre-existing neurodevelopmental disorders. Yet, the association of iron deficiency and neurodevelopmental disorders in childhood and adolescence has not yet been explored comprehensively. In this scoping review, we investigate 1) the association of iron deficiency in children and adolescents with the most frequent neurodevelopmental disorders, ADHD, ASD, and FASD, and 2) whether iron supplementation improves outcomes in these disorders. METHOD: Scoping review of studies published between 1994 and 2021 using "iron deficiency / iron deficiency anemia" AND "ADHD" OR "autism" OR "FASD" in four biomedical databases. The main inclusion criterion was that articles needed to have quantitative determination of iron status at any postnatal age with primary iron markers such as serum ferritin being reported in association with ADHD, ASD, or FASD. RESULTS: For ADHD, 22/30 studies and 4/4 systematic reviews showed an association of ADHD occurrence or severity with iron deficiency; 6/6 treatment studies including 2 randomized controlled trials demonstrated positive effects of iron supplementation. For ASD, 3/6 studies showed an association with iron deficiency, while 3/6 and 1/1 systematic literature review did not; 4 studies showed a variety of prevalence rates of iron deficiency in ASD populations; 1 randomized controlled trial found no positive effect of iron supplementation on behavioural symptoms of ASD. For FASD, 2/2 studies showed an association of iron deficiency with growth retardation in infants and children with prenatal alcohol exposure. CONCLUSION: Evidence in favor of screening for iron deficiency and using iron supplementation for pediatric neurodevelopmental disorders comes primarily from ADHD studies and needs to be further investigated for ASD and FASD. Further analysis of study methodologies employed and populations investigated is needed to compare studies against each other and further substantiate the evidence created.

Disruptive Behaviors and Intellectual Disability: Creating a New Script.

Background: Terms currently used to describe the so-called challenging and disruptive behaviors (CBDs) of children with intellectual disabilities (ID) have different connotations depending on guiding contextual frameworks, such as academic and cultural settings in which they are used. A non-judgmental approach, which does not attempt to establish existing categorical diagnoses, but which describes in a neutral way, is missing in the literature. Therefore, we tried to describe CDBs in youth with ID in an explorative study. Methods: Interviews with families investigated the CDBs of five youth with Down syndrome. At home, families tracked youth's sleep/wake behaviors and physical activity. Youth were observed in a summer school classroom. The collected information and suggested explanatory models for observed CDBs were reviewed with the families. Results: We grouped CDBs as challenging, if they were considered to be reactive or triggered, or unspecified, if no such explanatory model was available. A third category was created for light-hearted CDBs: goofy, acknowledging the right to laugh together with peers. We found some relationships between sleep, physical activity, and CDBs and developed an explorative approach, supporting a child-centered perspective on CDBs. Conclusion: The controversial discussions on terminology and management of CDBs in the literature demonstrate the need for a non-judgmental approach. Such an explorative approach, allowing non-professionals to not label, has been missing. The fact that, up to now, the light-hearted behaviors of an individual with ID have not been integrated in commonly-used behavioral checklists as their natural right, proves our concept and indicates that a paradigm change from judgment-based to exploratory-driven approaches is needed.

Revisiting the Concept of Vigilance.

Vigilance deficits can be observed after a period of prolonged, continuous wakefulness. In this context there has been extensive research targeting the impact of sleep deficits on different aspects of vigilance, but the underlying concept of vigilance was hardly ever addressed and discussed. One reason for this shortcoming is the unclear and ambiguous definition of the term vigilance, which is commonly used interchangeably with sustained attention and even wakefulness. This confusion is the result of a wide range of misleading definitions, starting in the 1940s, as psychologists redefined the concept of vigilance suggested by British Neurologist, Henry Head, in 1923. Nevertheless, the concept of vigilance is still useful and innovative, especially in treating sleep problems in children and young adults. This paper reviews the current usage of the term vigilance in sleep-wake-research and describes not only the benefits, but even more clearly, its limitations. By re-focusing on the definitions given by Henry Head, the concept of vigilance is an innovative way to gather new insights into the interplay between sleep- and daytime behaviors. In addition, future research on vigilance should consider three perspectives: 1st vigilance perceived as a process to allocate resources, 2nd vigilance associated with compensatory behaviors and 3rd the role of vigilance in human environmental interactions. This approach, understood as a conceptual framework, provides new perspectives by targeting sleep-wake behaviors as a 'real life' outcome measure, reflecting both physical and cognitive performance as well as sleep quality and quantity.

Sleep as an outcome measure in ADHD randomized controlled trials: A scoping review.

Sleep disturbances are highly prevalent among children with ADHD. Yet, diagnostic and treatment regimens are primarily focused on daytime symptomatology. The goals of this scoping review are to 1) identify interventional ADHD RCTs that have used sleep as an outcome measure, 2) describe and assess the validity of tools utilized to measure sleep-specific outcomes. 40/71 RCTs used sleep as a primary outcome. Actigraphy (n = 18) and sleep log/diary (n = 16) were the most common tools to measure sleep, followed by Children's Sleep Habits Questionnaire (n = 13), and polysomnography (n = 10). Sleep was a secondary outcome in 31 RCTs. Polysomnography and actigraphy used a heterogeneous spectrum of sleep-related variables and technical algorithms, respectively. 19/23 sleep questionnaires were validated covering a spectrum of sleep-related domains. Despite the intrinsic nature of sleep disturbances in ADHD, the number of RCTs measuring sleep-specific outcomes is limited and tools to measure outcomes are not standardized. Given the potential adverse effects of ADHD medications on sleep, sleep should be included as a core outcome measure in future clinical trials.

Children's Sleep During COVID-19: How Sleep Influences Surviving and Thriving in Families.

OBJECTIVE: The COVID-19 pandemic has the potential to disrupt the lives of families and may have implications for children with existing sleep problems. As such, we aimed to: (1) characterize sleep changes during the COVID-19 pandemic in children who had previously been identified as having sleep problems, (2) identify factors contributing to sleep changes due to COVID-19 safety measures, and (3) understand parents' and children's needs to support sleep during the pandemic. METHODS: Eighty-five Canadian parents with children aged 4-14 years participated in this explanatory sequential, mixed-methods study using an online survey of children's and parents' sleep, with a subset of 16 parents, selected based on changes in their children's sleep, participating in semi-structured interviews. Families had previously participated in the Better Nights, Better Days (BNBD) randomized controlled trial. RESULTS: While some parents perceived their child's sleep quality improved during the COVID-19 pandemic (14.1%, n = 12), many parents perceived their child's sleep had worsened (40.0%, n = 34). Parents attributed children's worsened sleep to increased screen time, anxiety, and decreased exercise. Findings from semi-structured interviews highlighted the effect of disrupted routines on sleep and stress, and that stress reciprocally influenced children's and parents' sleep. CONCLUSIONS: The sleep of many Canadian children was affected by the first wave of the COVID-19 pandemic, with the disruption of routines influencing children's sleep. eHealth interventions, such as BNBD with modifications that address the COVID-19 context, could help families address these challenges.

Fidgety Philip and the Suggested Clinical Immobilization Test: Annotation data for developing a machine learning algorithm.

The cartoon Fidgety Philip, the banner of Western-ADHD diagnosis, depicts a 'restless' child exhibiting hyperactive-behaviors with hyper-arousability and/or hypermotor-restlessness (H-behaviors) during sitting. To overcome the gaps between differential diagnostic considerations and modern computing methodologies, we have developed a non-interpretative, neutral pictogram-guided phenotyping language (PG-PL) for describing body-segment movements during sitting (Journal of Psychiatric Research). To develop the PG-PL, seven research assistants annotated three original Fidgety Philip cartoons. Their annotations were analyzed with descriptive statistics. To review the PG-PL's performance, the same seven research assistants annotated 12 snapshots with free hand annotations, followed by using the PG-PL, each time in randomized sequence and on two separate occasions. After achieving satisfactory inter-observer agreements, the PG-PL annotation software was used for reviewing videos where the same seven research assistants annotated 12 one-minute long video clips. The video clip annotations were finally used to develop a machine learning algorithm for automated movement detection (Journal of Psychiatric Research). These data together demonstrate the value of the PG-PL for manually annotating human movement patterns. Researchers are able to reuse the data and the first version of the machine learning algorithm to further develop and refine the algorithm for differentiating movement patterns.

Barriers and facilitators to treating insomnia in children with autism spectrum disorder and other neurodevelopmental disorders: Parent and health care professional perspectives.

BACKGROUND/AIMS: Insomnia is highly prevalent in children with neurodevelopmental disorders (NDDs), yet little research exists on sleep treatment access, utilization, and provision in this population. This study explores barriers and facilitators to access, use, and provision of treatment for sleep problems as experienced by parents of children with NDDs, including Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), Cerebral Palsy (CP) and Fetal Alcohol Spectrum Disorder (FASD), and health care professionals who work with children with these conditions. METHOD: Transcripts from online focus groups and interviews, conducted separately with parents of children with NDDs (n = 43) and health care professionals (n = 44), were qualitatively analyzed using content analysis for key themes. RESULTS: Barriers included limited access to/availability of treatment, lack of knowledge/training, NDD-specific factors (e.g., symptoms, medications, and comorbidities), parent factors (e.g., capacity to implement treatment, exhaustion), and the challenging, intensive nature of sleep treatment. Facilitators included positive beliefs and attitudes, education, support, and ability to modify treatments for NDD symptoms. Barriers and facilitators were similar across all four NDDs. CONCLUSIONS: Results highlight a need for more education about sleep in NDDs and to develop accessible interventions, as well as the potential of a transdiagnostic approach to sleep treatment in this population.

Is Fidgety Philip's ground truth also ours? The creation and application of a machine learning algorithm.

BACKGROUND: Behavioral observations support clinical in-depth phenotyping but phenotyping and pattern recognition are affected by training background. As Attention Deficit Hyperactivity Disorder, Restless Legs syndrome/Willis Ekbom disease and medication induced activation syndromes (including increased irritability and/or akathisia), present with hyperactive-behaviors with hyper-arousability and/or hypermotor-restlessness (H-behaviors), we first developed a non-interpretative, neutral pictogram-guided phenotyping language (PG-PL) for describing body-segment movements during sitting. METHODOLOGY & RESULTS: The PG-PL was applied for annotating 12 1-min sitting-videos (inter-observer agreements >85%->97%) and these manual annotations were used as a ground truth to develop an automated algorithm using OpenPose, which locates skeletal landmarks in 2D video. We evaluated the algorithm's performance against the ground truth by computing the area under the receiver operator curve (>0.79 for the legs, arms, and feet, but 0.65 for the head). While our pixel displacement algorithm performed well for the legs, arms, and feet, it predicted head motion less well, indicating the need for further investigations. CONCLUSION: This first automated analysis algorithm allows to start the discussion about distinct phenotypical characteristics of H-behaviors during structured behavioral observations and may support differential diagnostic considerations via in-depth phenotyping of sitting behaviors and, in consequence, of better treatment concepts.

Treatment algorithm for the use of psychopharmacological agents in individuals prenatally exposed to alcohol and/or with diagnosis of fetal alcohol spectrum disorder (FASD).

Psychotropic medication treatment of individuals who have experienced prenatal alcohol exposure (PAE) has lagged behind psychosocial interventions. Multiple psychotropic medications are often prescribed for those diagnosed with a range of neurodevelopmental disabilities and impairments of PAE (neurodevelopmental disorder associated with prenatal alcohol exposure and/or fetal alcohol spectrum disorder [ND-PAE/FASD]). Despite the diverse comorbid mental disorders, there are no specific guidelines for psychotropic medications for individuals with ND-PAE/FASD. When prescribed, concerned family members and caregivers of individuals with ND-PAE/FASD reported that polypharmacy, which was typical and adverse effects render the psychotropic medications ineffective. The objective of this work was to generate a treatment algorithm for the use of psychopharmacological agents specifically for individuals with ND-PAE/FASD. The development of decision tree for use to prescribe psychotropic medications incorporated findings from previous research and the collective clinical experience of a multidisciplinary and international panel of experts who work with individuals with ND-PAE/FASD, including an algorithm specialist. After multiple meetings and discussions, the experts reached consensus on how best to streamline prescribing along neurodevelopmental clusters. These were subdivided into four ligand-specific, receptor-acting medication targets (hyperarousal, emotional dysregulation, hyperactive/neurocognitive, and cognitive inflexibility). Each cluster is represented by a list of common symptoms. The experts recommended that prescribers first ensure adequate psychosocial and environmental, including sufficient dietary, exercise, and sleep support before prescribing psychotropic medications. Treatment then progresses through three steps of psychotropic medications for each cluster. To support established treatment goals, the most function impairing clusters are targeted first.

Iron deficiency and sleep - A scoping review.

Iron deficiency (ID) is associated with sleep disorders, but standardized assessment of iron status in the diagnostic work-up and iron supplementation as treatment have not been considered in clinical practice. We investigated associations of ID with type and severity of sleep disorders and whether iron supplementation improves sleep-related symptoms. In 2017, we conducted a scoping review for the period 1972-2016 using the terms "iron deficiency anemia" and "sleep" on biomedical database search engines, and in 2019, we updated our review with an ad-hoc search. Among the 93 articles meeting our inclusion criteria, 74/93 studies investigated restless legs syndrome (RLS), 8/93 periodic limb movements in sleep (PLMs), 3/93 sleep disordered breathing (SDB), 6/93 general sleep disturbances (GSD), and 2/93 attention-deficit/ hyperactivity disorder related sleep disorders (ADHD-SDs). A statistically supported positive association with ID was found in 22/42 RLS, 3/8 PLMs, 1/2 SDB, 3/4 GSD, and 1/2 ADHD-SDs association studies. The ad-hoc literature search revealed eight additional association studies with a statistically supported positive association in 2/5 RLS, 1/1 SDB, 1/1 ADHD-SDs, and 1/1 restless sleep disorder (RSD) studies. Iron supplementation was beneficial in 29/30 RLS (including five randomized controlled trials [RCTs]), 1/1 SDB, and 2/2 GSD treatment studies. Iron supplementation was also beneficial in 2/2 RLS (including two RCTs), 1/1 GSD (RCT), and 1/1 RSD studies identified in the ad-hoc search. In pediatric populations, 1/1 RLS, 1/1 SDB, 2/5 PLMs, 2/3 GSD and 1/2 ADHD-SDs studies found positive associations, and 6/6 RLS and 2/2 GSD studies demonstrated a benefit with iron supplementation. In conclusion, iron investigation and supplementation should be considered in patients presenting with sleep disorders. To investigate the role of ID in sleep in the future, a harmonization of study designs, including outcome measures and standardized iron and inflammation status is necessary.