The Role of Supplements and Over-the-Counter Products to Improve Sleep in Children: A Systematic Review.

The sleep-wake cycle is a complex multifactorial process involving several neurotransmitters, including acetylcholine, norepinephrine, serotonin, histamine, dopamine, orexin and GABA, that can be, in turn, regulated by different nutrients involved in their metabolic pathways. Although good sleep quality in children has been proven to be a key factor for optimal cognitive, physical and psychological development, a significant and ever-increasing percentage of the pediatric population suffers from sleep disorders. In children, behavioral interventions along with supplements are recommended as the first line treatment. This systematic review was conducted, according to the PRISMA guidelines, with the purpose of assessing the principal nutrients involved in the pathways of sleep-regulating neurotransmitters in children and adolescents. Our focus was the utilization of over the counter (OTC) products, specifically iron, hydroxytryptophan, theanine and antihistamines in the management of different pediatric sleep disorders with the intention of providing a practical guide for the clinician.

Surfactant protein D concentration in a pediatric population with suspected sleep disorder.

Obstructive sleep apnea (OSA) affects between 2% and 4% in children and there is a search for new biomarkers that can be useful both in the diagnosis and in the evolution of the disease. The surfactant protein D (SP-D) is a collection that is part of the innate immune system exerting an anti-inflammatory and antimicrobial effect. Thus, the objective of this study was to evaluate the concentration of SP-D in the suspect OSA pediatric population. A total of 178 children were recruited in this prospective study. Blood samples, sleep parameters, feeding habits, anthropometric, sociodemographic, and family data were collected. Specific biochemical determinations were made, and the plasmatic concentrations of SP-D were measured by enzyme-linked immunosorbent assay. We found no statistical correlation between the SP-D concentration and the apnea-hypopnea index (AHI) from the data. Nevertheless, the changes in SP-D levels could be correlated to a large extent by the arousals that often go along with hypopneas (r = -0.258, p = 0.011 unadjusted; r = -0.258, p = 0.014 adjusted by age and body mass inded [BMI] Z-score). Intermittent hypoxia was correlated with C-reactive protein levels (r = 0.547, p < 0.001 unadjusted; r = 0.542, p < 0.001 adjusted by age and BMI Z-score). Although AHI and SP-D did not appear to correlate, a secondary analysis suggests that sleep fragmentation, which is produced by arousals, may do, and further research is needed to determine the mechanisms by which changes in SP-D occur in OSA.

Polysomnographic Characteristics of Snoring Children: A Familial Study of Obstructive Sleep Apnea Syndrome.

BACKGROUND AND OBJECTIVES: Available evidence suggests a familial basis for OSA. The aim of the present study was to assess the potential influences of parental OSA in predicting the diagnosis and severity of OSA in snoring children. METHODS: Observational study, we prospectively enrolled 84 children and their parents. A complete nocturnal polysomnography was performed. Children were categorized into 3 severity groups according to the apnea-hypopnea index (AHI<1h-1, AHI≥1h-1 to AHI<5h-1, and AHI≥5h-1). Adults were grouped according two criteria (AHI≥5h-1 and ≥10h-1). RESULTS: There were no significant differences in age, gender, BMI and BMI z-score among groups. Among the children, 54.7% had an AHI≥1h-1 and 21.4% had an AHI≥5h-1. Overall, we observed that 60.7% of fathers and 23.8% of mothers of our population had OSA (AHI≥5h-1). The prevalence of fathers with OSA increases with the children's severity (83% in the group of children with moderate-severe OSA, p=0.035). The odds of having moderate-severe pediatric OSA (AHI≥5h-1) were more than 4 times higher among children with a father with AHI≥5h-1 (OR: 4.92, 95% CI: 1.27-19.06; p=0.021). There was no evidence of any maternal influence on OSA severity among the children studied. CONCLUSIONS: Our findings suggest a high prevalence of OSA among the family members studied with an increased association of childhood OSA with paternal OSA. Prediction of OSA risk among children can be significantly improved by adding data on paternal OSA status.

Associations among sleep symptoms, physical examination, and polysomnographic findings in children with obstructive sleep apnea.

PURPOSE: The relationships among PSG findings, OSA symptoms, and tonsil and adenoid size are not clear. In this study, we aimed to investigate the associations between pediatric OSA and tonsil and adenoid size using subjective (OSA-18 questionnaire) and objective (PSG) measurements. METHODS: 101 consecutive patients aged from 2 to 12 years (mean age, 5.4 ± 2.2 years; boys, 72.3%) diagnosed with OSA were enrolled in two age groups (2-6 years group and 7-12 years group) and underwent PSG and lateral cephalometric radiography. Tonsil size and the adenoid-nasopharyngeal (A/N) ratio were determined. Quality of life and sleep symptoms were measured using the Chinese version OSA-18 questionnaire. Demographic and clinical data were obtained. RESULTS: 75 and 26 patients were separately enrolled in 2-6 years group and 7-12 years group. In 2-6 years group, the multiple linear regression revealed that tonsil size and A/N ratio were associated with log apnea-hypopnea index (AHI), and the Spearman's rank correlation reflected a positive correlation between log AHI and the OSA-18 sleep disturbance score (r = 0.362, P = 0.001). Log OSA-18 score was correlated with tonsil size (r = 0.349, P = 0.002) but not the A/N ratio in 2-6 years group. Finally, no significant associations were observed between log OSA-18 scores and log AHI in all patients. CONCLUSION: As PSG stays the golden standard for diagnoses of pediatric OSA, physical examinations and quality-of-life assessments are needed to fully assess the impact of OSA on children.

Prothrombotic state in children with obstructive sleep apnea.

OBJECTIVE: Increased blood coagulation might be one important mechanism linking obstructive sleep apnea (OSA) with cardiovascular diseases. We tested the association between several hemostatic parameters and sleep breathing-related variables in a representative pediatric population with a clinical suspicion of OSA. METHODS: Polysomnography was performed in 152 snoring children to diagnose OSA. Anthropometric and clinical data were registered and venous blood samples were collected for the measurement of platelet count, plateletcrit, platelet distribution width (PDW), mean platelet volume (MPV), prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and C-reactive protein. RESULTS: Children with OSA had significantly higher platelet count, plateletcrit and PDW compared with those without OSA. After controlling for the anthropometric characteristics (age, gender, body mass index (BMI) z-score), platelet count negatively correlated with minimum SaO2 while the plateletcrit correlated with time with SaO2 <90% and MPV correlated with apnea-hypopnea index. PT and PT international normalized ratio correlated with mean SaO2 and aPTT correlated with the oxygen desaturation index. CONCLUSION: Our findings suggest that different OSA-related effects may be factors contributing to an enhanced coagulability in pediatric OSA. Measures reflecting apnea severity and disrupted sleep were associated with clotting factor changes independent of covariates affecting hemostatic function.

Glycated hemoglobin and sleep apnea syndrome in children: beyond the apnea-hypopnea index.

PURPOSE: Snoring and obstructive sleep apnea syndrome (OSA) are frequent conditions in pediatrics. Glycated hemoglobin (HbA1C) is a useful homeostatic biomarker of glycemia and may reflect alterations deriving from sleep breathing disorders. The aim of this study was to relate the severity of OSA with blood HbA1C levels in children. METHODS: A descriptive observational study in snoring patients was performed. All patients underwent a sleep study and classified either as simple snorers (apnea-hypopnea index; AHI ≤ 1 episodies/h) or as OSA patients (AHI > 1 episodes/h). In the following morning, a blood glycemic profile (fasting glucose, insulin, HbA1C, and the HOMA index) was performed to every individual. RESULTS: A total of 48 patients were included. HbA1C levels were shown to be increased in the moderate OSA (AHI > 5 episodes/h) group (5.05 ± 0.25 vs. 5.24 ± 0.29%; p = 0.019). Significant correlations were found between HbA1C values and AHI (r = 0.345; p = 0.016) and also with oxygen desaturation index (r = 0.40; p = 0.005). Correlations remained significant after adjusting by age and body mass index. The AHI-associated change in HbA1C was 13.4% (p = 0.011). CONCLUSIONS: In the pediatric population, HbA1C is a biomarker associated with OSA severity, and this relationship is age- and obesity-independent. The fact that this association was observed in snoring patients could help the physician in the distinction between those patients affected with OSA and those with simple snoring. Therefore, HbA1C measurement could play a major role in the diagnosis and the management of the syndrome.

Circulating branched-chain amino acids in children with obstructive sleep apnea.

INTRODUCTION: The effects of obstructive sleep apnea (OSA) on the metabolic system are not well understood, especially in children. Recent studies have provided evidence of the modulation of insulin action by branched-chain amino acids (BCAAs) and suggested novel mechanistic relationships between glucose and amino acid metabolic pathways. We hypothesized that plasma BCAA levels may serve as biomarkers of insulin resistance and metabolic dysfunction in children with OSA. METHODS: A polysomnography was conducted for the diagnosis of OSA in 90 snoring children, in a tertiary hospital. Anthropometric and clinical data were measured and venous blood samples were collected for the measurement of plasma glucose, insulin, HbA1c, and amino acids. RESULTS: Children with OSA had significantly higher levels of BCAAs (leucine, isoleucine, and total BCAAs) compared with those without OSA (P = 0.024). A positive significant correlation was observed between insulin levels and both leucine and isoleucine (r = 0.232; P < 0.05). On multivariate regression analyses, the presence of OSA was significantly associated with leucine, isoleucine, and total BCAA concentrations (P = 0.028), whereas the arousal index was associated with leucine, valine, and total BCAA levels (P = 0.037). CONCLUSIONS: The presence of OSA and sleep fragmentation may induce changes in branched-chain amino acid metabolism in snoring children, independently of obesity. These data may suggest a new mechanism linking OSA and glucose homeostasis.

The Development of Sleep Medicine: A Historical Sketch.

ABSTRACT: For centuries the scope of sleep disorders in medical writings was limited to those disturbances which were either perceived by the sleeper him- or herself as troublesome, such as insomnia, or which were recognized by an observer as strange behavioral acts during sleep, such as sleepwalking or sleep terrors. Awareness of other sleep disorders, which are caused by malfunction of a physiological system during sleep, such as sleep-related respiratory disorders, were widely unknown or ignored before sleep monitoring techniques became available, mainly in the second half of the 20(th) century. Finally, circadian sleep-wake disorders were recognized as a group of disturbances by its own only when chronobiology and sleep research began to interact extensively in the last two decades of the 20(th) century. Sleep medicine as a medical specialty with its own diagnostic procedures and therapeutic strategies could be established only when key findings in neurophysiology and basic sleep research allowed a breakthrough in the understanding of the sleeping brain, mainly since the second half of the last century.

The family role in children׳s sleep disturbances: Results from a cross-sectional study in a Portuguese Urban pediatric population.

BACKGROUND: Sleep Disorders (SlD) are frequently undervalued complaints in childhood. Several factors influence sleep, particularly socio-cultural environment and medical conditions such as breathing disorders. Poor sleep hygiene has physical, educational and social consequences. In Portugal, there are few published studies about children׳s sleep habits and rarely based on validated questionnaires. AIM: To study the prevalence of SlD and associated factors, in an outpatient pediatric population of a Primary Health Care Center (PHCC). METHODS: Cross-sectional study of children admitted to a PHCC on a suburban area of Lisbon. Children Sleep Habits Questionnaire, validated for the Portuguese population (CSHQ-PT) for the screening of SlD (cut-off=44), was applied to parents, as well as a demographic inquiry. Body mass index z-score was evaluated. Children scoring 44 or above were sent to Pediatric Sleep Disorders consultation (PSDC). Parametric and non-parametric tests were used whenever appropriate. RESULTS: From 128 children, 57.8% were male; the median age was 6.0 years (P 25=5.0; P 75=8.0). The median of cohabitants per family was 4.0 (P 25=3.0; P 75=5.0); 21.1% lived in a single-parent family. From CSHQ-PT, 59.4% (76) scored above the cut-off. Data showed that children from a single-parent family have more SlD (p=0.048), particularly parasomnia (p=0.019). Children with sleep disordered breathing (SDB) suffer more daytime sleepiness (p=0.034). From 63 children sent to PSDC, 33 attended. Regarding these children, a difference was found between BMI z-scores of those with and without SDB (p=0.06). CONCLUSION: Family structure plays a non-negligible role in children's sleep habits. Daily performance of children with SDB may become compromised.

Assessment and treatment of obstructive sleep-disordered breathing.

Obstructive sleep-disordered breathing (OSDB) is a condition that affects 1% to 3% of the pediatric population. These disorders are difficult to diagnosis and left untreated may be serious, including not only medical comorbidities but also cognitive, academic, behavioral, and emotional sequelae. This article is designed to bring awareness of the severity and prevalence to family physicians and pediatricians. It reviews detailed information concerning OSDB, including the predisposing factors, assessment of presenting features, and treatment.