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      Pediatric sleep disturbances and treatment with melatonin

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          Abstract

          Background

          There are no guidelines concerning the best approach to improving sleep, but it has been shown that it can benefit the affected children and their entire families. The aim of this review is to analyse the efficacy and safety of melatonin in treating pediatric insomnia and sleep disturbances.

          Main body

          Sleep disturbances are highly prevalent in children and, without appropriate treatment, can become chronic and last for many years; however, distinguishing sleep disturbances from normal age-related changes can be a challenge for physicians and may delay treatment. Some published studies have shown that melatonin can be safe and effective not only in the case of primary sleep disorders, but also for sleep disorders associated with various neurological conditions. However, there is still uncertainty concerning dosing regimens and a lack of other data. The dose of melatonin should therefore be individualised on the basis of multiple factors, including the severity and type of sleep problem and the associated neurological pathology.

          Conclusions

          Melatonin can be safe and effective in treating both primary sleep disorders and the sleep disorders associated with various neurological conditions. However, there is a need for further studies aimed at identifying the sleep disordered infants and children who will benefit most from melatonin treatment, and determining appropriate doses based on the severity and type of disorder.

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          Most cited references65

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          New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

          In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24 h light–dark cycle to invigorate and optimize the internal temporal order. The SCN‐activated, light‐inhibited production of melatonin conveys the message of darkness to the clock and induces night‐state physiological functions, for example, sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo‐controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, for example, circadian rhythm‐related sleep disorders, jet lag and shift work, insomnia in children with neurodevelopmental disorders, poor (non‐restorative) sleep quality, non‐dipping nocturnal blood pressure (nocturnal hypertension) and Alzheimer's disease (AD). The diminished production of melatonin at the very early stages of AD, the role of melatonin in the restorative value of sleep (perceived sleep quality) and its sleep‐anticipating effects resulting in attenuated activation of certain brain networks are gaining a new perspective as the role of poor sleep quality in the build‐up of β amyloid, particularly in the precuneus, is unravelled. As a result of the recently discovered relationship between circadian clock, sleep and neurodegeneration, new prospects of using melatonin for early intervention, to promote healthy physical and mental ageing, are of prime interest in view of the emerging link to the aetiology of Alzheimer's disease. Linked Articles This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc
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            The basic physiology and pathophysiology of melatonin.

            Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal environmental conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone can be determined by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body physiology. This information is used for the organisation of functions, which respond to changes in the photoperiod such as the seasonal rhythms. Seasonal rhythmicity of physiological functions in humans related to possible alteration of the melatonin message remains, however, of limited evidence in temperate areas in field conditions. Also, the daily melatonin secretion, which is a very robust biochemical signal of night, can be used for the organisation of circadian rhythms. Although functions of this hormone in humans are mainly based on correlative observations, there is some evidence that melatonin stabilises and strengthens coupling of circadian rhythms, especially of core temperature and sleep-wake rhythms. The circadian organisation of other physiological functions could depend on the melatonin signal, for instance immune, antioxidative defences, hemostasis and glucose regulation. Since the regulating system of melatonin secretion is complex, following central and autonomic pathways, there are many pathophysiological situations where the melatonin secretion can be disturbed. The resulting alteration could increase predisposition to disease, add to the severity of symptoms or modify the course and outcome of the disorder.
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              Sleep problems in autism spectrum disorders: prevalence, nature, & possible biopsychosocial aetiologies.

              As considerably more people are diagnosed with an autism spectrum disorder (ASD), interest in the associated behaviours, including sleep problems has increased. This has resulted in a subsequent increase in the research related to the sleep problems occurring in people with an ASD. This article summarizes and evaluates the current literature related to a) the higher prevalence of a sleep problem compared to typically developing children, b) the specific types of sleep problems for people with an ASD, and c) the possible aetiology of sleep problems in the ASDs within a biopsychosocial framework. It is concluded that recent studies confirm that the majority of this population are likely to experience sleep difficulties, with settling issues in children with an ASD the most commonly reported. However, exploration of the types of sleep difficulties and associated aetiological factors in the ASDs is still in its infancy.
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                Author and article information

                Contributors
                +39 075 5784417 , susanna.esposito@unimi.it
                Daniela.laino@hotmail.it
                renatodolphin1985@gmail.com
                almiomedico@libero.it
                lory.digenova@gmail.com
                antonella.fattorusso@libero.it
                aargentiero85@gmail.com
                elisabetta.mencaroni@ospedale.perugia.it
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                12 March 2019
                12 March 2019
                2019
                : 17
                : 77
                Affiliations
                [1 ]ISNI 0000 0004 1757 3630, GRID grid.9027.c, Pediatric Clinic, Department of Surgical and Biomedical Sciences, , Università degli Studi di Perugia, ; Piazza Menghini 1, 06129 Perugia, Italy
                [2 ]ISNI 0000 0004 1757 2822, GRID grid.4708.b, Department of Pathophysiology and Transplantation, , Università degli Studi di Milano, ; Milan, Italy
                Author information
                http://orcid.org/0000-0003-4103-2837
                Article
                1835
                10.1186/s12967-019-1835-1
                6419450
                30871585
                ef31d95c-500e-483d-8382-d3c8e6bb6805
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 December 2018
                : 6 March 2019
                Funding
                Funded by: World Association of Infectious Diseases and Immunologcal Disorders grant
                Award ID: WAidid2018_02
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Medicine
                attention-deficit/hyperactivity disorder,autism spectrum disorders,insomnia,melatonin,neurodevelopmental disabilities,sleep disturbances

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