The clinical picture of children with autism spectrum disorder (ASD) is characterized by deficits of social interaction and communication as well as by repetitive interests and activities, according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition.1 The diagnosis of ASD remains clinical and no reliable biomarkers are available. Prevalence is 16.8 per 1,000 children age 8 years and older.2
Sleep disorders are one of the most frequent comorbidities reported in ASD,3 leading to the use of a considerable amount of resources for medical examinations and treatments. The care of these disorders in children with ASD involves various health professionals, starting with the pediatrician. It should be noted that sleep disorders increase the risk for physical health problems involving the cardiovascular, immune, and endocrine systems, which is particularly important in children with ASD as they have a higher risk of overweight and obesity.4–6
In this article, we review the main features of sleep disorders in children with ASD and their implications for patients and their families.
Sleep Problems in Children with ASD
Sleep problems are more frequent in children with ASD than in typically developed children.7 Insomnia is present in children with ASD at all cognitive levels, with a prevalence that could reach 60% to 86%, which is 2 to 3 times higher than that seen in typically developed children.8 By definition, insomnia is characterized by significant difficulties initiating and/or maintaining sleep, and in children it manifests with bedtime refusal, difficulty falling asleep after “lights out,” and frequent night awakenings.9
Taira et al.,10 in 1998, using questionnaires completed by parents, found that 56 of 88 children with ASD (63.6%) had sleep disorders (with 44 children presenting before age 3 years). The most common sleep problems weredifficulty falling asleep (26.1%), frequent awakening during sleep time (21.6%), and early morning awakening (12.5%). Enuresis, considered separately, was present in 25%. Sleep disorders resolved at an average age of 5 years, and the authors hypothesized that sleep improvement could be attributed to lifestyle changes such as the entry into kindergarten or elementary school.10 However, it is likely that these conclusions concerning the evolution of sleep disorders were too optimistic, probably due to a short follow-up. In fact, other studies in the following years showed that sleep disorders in children with ASD tend to persist into adulthood.6
Gail Williams et al.,11 in 2004, studied 210 children with ASD through a questionnaire for parents. The most frequent sleep problems were difficulty falling asleep (53.3%), restless sleep (40.0%), unwillingness to fall asleep in own bed (39.5%), frequent awakenings (33.8%), difficulty arousing (31.5%), enuresis (27.7%), disoriented waking (27.1%), daytime mouth breathing (25.7%), excessive daytime sleepiness (23.3%), bruxism (21.0%), and snoring (21.0%). No significant differences were found in the frequency of reported problems between participants with and without intellectual disability (ID) except for night awakening, which was much more frequent in the group with ID. Nocturnal enuresis was a significantly occurrence in younger people.11
Liu et al.,12 in 2006, using a questionnaire completed by parents, found that 86% of 167 children with ASD suffered from sleep problems almost every day. Sleep disorders included insomnia in 56%, bedtime resistance in 54%, parasomnias in 53%, morning rising problems in 45%, daytime sleepiness in 31%, and sleep disordered breathing in 25%. A series of factors were associated with sleep disorders: younger age, hypersensitivity, co-sleeping, epilepsy, attention-deficit/hyperactivity disorder (ADHD), asthma, bedtime ritual, medication use, and family history of sleep disorders. Furthermore, comorbid epilepsy, insomnia, and parasomnias were associated with an increased risk for daytime sleepiness.12
Krakowiak et al.,13 in 2008, using questionnaires for parents, found at least one frequent sleep problem in 53% of the 303 children with ASD in the study (in 46% of 63 children with developmental delay and in 32% of 163 typically developed children; P < 0.0001). In children with ASD, sleep onset problems prevailed marginally and night waking prevailed significantly compared to the typical development group. The group with developmental delay presented with an intermediate situation between children with ASD and typical development groups. Cognitive or adaptive development was not predictive of the severity of sleep problems in the ASD group.13
Köse et al.,14 in 2017, through a questionnaire for parents, studied sleep problems in 48 children with ASD, in 46 children with ID without ASD, and in 48 children with typical development. No significant differences were found between the ID and ASD groups, and sleep disturbances prevailed in the children with ASD and children with ID compared to those with typical development. The risk of sleep problems was increased by co-sleeping with parents and by a family history of sleep disorders.14 The results of this study support the hypothesis that the frequent and heterogeneous sleep disorders described above are not specific to ASD but belong to a larger group of neurodevelopmental disorders.15
The Impact of Sleep Disorders on Daytime Activities
Sleep is a critical factor for typical synaptic development and brain maturation, so poor sleep can cause harmful effects on cognitive functions of children in several domains, such as attention, memory, mood regulation, and behavior. These negative daytime effects may be even more severe in children with neurodevelopmental disorders, including in children with ASD, than in the general population.8,16 Mazurek and Sohl,17 in 2016, found in a study of 81 children with ASD that sleep disorders were significantly associated with behavioral dysregulation consisting of physical aggression, irritability, inattention, and hyperactivity. Night awakenings showed the strongest association with daytime behavior problems, even after controlling for age and sex.17
Cohen et al.,18 in 2018, studied the possible relationship between poorer sleep quality and increased severity of daytime challenging behavior (eg, aggression, self-injury, tantrums, and property destruction) in 67 people with low-functioning ASD. The authors, analyzing data from more than 20,000 nights, found a statistically significant predictive relationship between sleep patterns and challenging daytime behavior in 81% of participants (P < 0.05). These findings lead us to hope that one day a real-time monitoring tool to prevent behavioral problems in people with ASD will be available.18
Some studies suggest that sleep disorders can also be related to the severity of the ASD core symptoms. A smaller number of sleep hours per night would be associated with more evident characteristics typical of ASD, including communication problems, stereotypic behavior, and hypersensitivity to the environment.6 Recently, Yang et al.,19 studying a sample of 169 children with ASD, found that those with sleep problems, compared to those without, showed worse daily living skills, social cognition and communication, and intellectual development. However, the meaning of the association between sleep disorders and ASD core symptoms is not clear. Is it possible that a greater severity of the ASD core symptoms predisposes to the occurrence of sleep disorders? Or, on the contrary, is it possible that the same sleep disorders accentuate or even provoke the appearance of the ASD core symptoms? This latter hypothesis has been considered only recently through systematic studies, which are discussed in the following text.
Could Sleep Disorders Precede the Appearance of ASD?
Alexeeff et al.,3 in 2017, found in their large sample of 3,911 people with ASD versus 38,609 controls that sleep disorders recurred in a minority of cases before the ASD diagnosis, and they were significantly associated with an increased risk of ASD as well as other numerous and heterogeneous medical conditions. Therefore, based on this study, it could be hypothesized that in a minority of people with ASD that sleep disorders play a pathogenic role.
Nguyen et al.,20 in 2018, using data from 1,096 children and their mothers included in a longitudinal birth cohort study, examined prospective associations between infant sleep characteristics at 12 months and ASD screening scores at 24 months while controlling for other psychosocial features. Infants who had more sleep problems at 12 months, particularly those with more night awakenings, showed a higher number of ASD symptoms at 24 months. The authors concluded that infant sleep features could be one clinical sign of ASD risk.20 The longitudinal nature of this study gives a considerable reliability to its results.
Verhoeff et al.,21 in 2018, aimed at understanding if sleep problems antecede and worsen autistic symptoms or occur as a result of ASD. They performed repeated sleep measures respectively at the age of 1.5, 3, 6, and 9 years in 5,151 children enrolled in a prospective birth cohort study. This cohort included 81 children with ASD. Sleep problems do not antecede and worsen ASD symptoms but rather co-occur with ASD symptoms in early childhood. Over time, children with ASD showed an increase in sleep problems, whereas typically developed children showed a decrease. The authors concluded by suggesting that sleep problems are part of the ASD construct.21
The apparently conflicting results of these few studies do not allow us to ascertain if sleep disorders may have a pathogenic role in the appearance of core autistic symptoms; therefore, further research is necessary in this field.
Hypotheses for the Etiology of Sleep Disorders in Children with ASD
The etiology of sleep disorders in children with ASD is multifactorial and related to complex interactions between biological factors (genetic, immunological, neurological) and psychological, socio-environmental, and family factors, including habits of care that are not always optimal.8,16,22 In turn, sleep disorders foster increased parental stress and sleep disruption.16,22,23Figure 1 summarizes the pathogenic mechanisms involved in sleep disorders of children with ASD. The following text summarizes the main etiopathogenetic hypotheses concerning insomnia in children with ASD.
Pathogenic mechanisms involved in sleep disorders of children with autism spectrum disorder. Each arrow indicates a predisposing effect, either established (solid line) or hypothesized (dotted line).
To begin, we should mention the presence of alterations in the organization and maturation of brain electrogenesis identified by polysomnography (an objective measure of sleep architecture that is usually performed in a laboratory and records many physiological parameters6). Several alterations have been reported, such as decreased time in bed and total sleep time, increased proportion of stage 1 sleep, longer sleep onset latency, reduced sleep efficiency (ie, the ratio of the total sleep time to the time spent in bed multiplied by 100), increased awakenings after sleep onset, and especially a deficit of rapid eye movement sleep. Overall, these findings suggest the presence of complex biological alterations impairing sleep quality in children with ASD.7,8 However, because these findings are heterogeneous and not constant, an ASD biomarker in brain electrogenesis during sleep is not available.
Another hypothesis focuses on changes in melatonin. A combination of reduced production, increased breakdown, and abnormal receptor sites of melatonin (probably on a genetic basis) may explain prolonged sleep latency and night awakenings in children with ASD. The favorable data concerning the treatments with exogenous melatonin support this hypothesis.8
Other possible causative factors of insomnia are represented by the hyperarousal and the sensory hyper-reactivity that cause unusual responses to sensory stimuli in a high percentage of children with ASD.8 Due to sensory abnormalities, environmental variables such as temperature, noise levels, and visual stimuli in the bedroom could negatively affect sleep; also, some textures of bed linen and pajamas can irritate the child and disturb their sleep.22 An involvement of the locus coeruleus-norepinephrine system could explain both hyperarousal and sensory dysregulation, as well as cognitive impairment in ASD. The excessive stimulation of this system, which may derive from regions such as the prefrontal cortex and the amygdala, could contribute to insomnia. In this perspective, it would not be a coincidence that the child with ASD and hyperarousal has behavioral symptoms such as inattention, impulsivity, overactivity, anxiety, and panic, as well as insomnia.8
Vitamin D is necessary for embryogenesis (ie, the development of the nervous system) and also for the activation of some genes. During pregnancy, a deficit of this vitamin may be an environmental risk factor for the development of ASD.24 At the same time, there seems to be a link between vitamin D deficit and insomnia, at least in adulthood.25
The preoptic area of the hypothalamus promotes sleep by using gamma-aminobutyric acid (GABA) as a neurotransmitter. In people with ASD, an impairment of the migration and maturation of GABA-ergic interneurons has been hypothesized.7 Perhaps it is no coincidence that a region of genetic susceptibility to autism, identified on the 15q chromosome, includes genes related to GABA.7
Regardless of the etiopathogenetic hypotheses, for a clinical perspective it is essential to evaluate carefully any medical condition that may affect sleep, such as gastrointestinal disorders (gastroesophageal reflux), respiratory disorders (breathing-related sleep disorders including obstructive sleep apnea), neurological disorders (epilepsy, restless legs syndrome), and skin disorders (eczema/itching), just to name a few.8
The role of adequate sleep hygiene should not be forgotten. van der Heijden et al.,26 in 2018, using parental questionnaires, found that sleep problems were highly prevalent in 44 children with ADHD and 68 children with ASD (63.6% and 64.7%, respectively) versus 243 typically developed children (25.1%). However, whereas sleep problems in children with ASD were related to poor sleep hygiene (see behavioral and environmental practices impairing sleep quality, such as caffeine use), in children with ADHD they were related to evening chronotype, and in children with typical development both factors were important.26 The limited size of the ADHD and ASD groups suggests these findings need to be verified in larger samples.
Management of Sleep Disorders in Children with ASD
The meta-synthesis of Cuomo et al.27 in 2017 examined eight systematic reviews (based on 38 original studies) regarding the efficacy of sleep interventions in children with ASD. The study considered 17 different areas of sleep disorders. The included reviews considered five main groups of sleep interventions: (1) melatonin; (2) other pharmacological treatments including secretin, risperidone, alpha2-adrenergic receptor agonists (clonidine), and benzodiazepines (clonazepam); (3) behavioral interventions consisting in combinations of a number of principles, including extinction (“planned ignoring”), sleep hygiene (eg, avoidance of “arousing” activities prior to bedtime) and positive reinforcement (use of rewards); (4) parent education or education program interventions characterized by a psychosocial educational component and conducted through various formats (home visits, phone contacts, handbooks); and (5) alternative therapies, including massage therapy, aromatherapy, multivitamin use, and iron supplementation. No single treatment was effective for all sleep problems in children with ASD. However, melatonin, behavioral interventions, and parent education or education programs seemed to be the most effective treatments for multiple domains of sleep problems.27
Based on our clinical experience, the oral administration of niaprazine, a histamine H1-receptor antagonist with remarkable sedative properties, could be very effective as a hypno-inducing drug in children and adolescents with ASD with insomnia, and it has an excellent level of safety.28 The most important recommendation is to avoid its use in individuals with a prolonged QTc interval on an electrocardiogram.
However, according to Ameis et al.,29 we reaffirm the importance that interventions with emerging evidence, including melatonin, should be considered after any medical conditions potentially contributing to sleep disorders have been carefully evaluated.
Many heterogeneous findings seem to differentiate the sleep of children with ASD from that of typically developed children. The heterogeneity of sleep disorders reported in the literature is not surprising given the methodological differences among the studies and particularly the differences among the ASD samples investigated.
There is great evidence that impaired sleep can negatively affect cognitive, emotional, and behavioral functioning. Therefore, an early screening and consequently a timely treatment of sleep disorders in children with ASD are essential for their care, as well as for the physical and psychological well-being of the family. Although the screening of sleep disorders can be performed through a brief clinical interview or a questionnaire (subjective tools), the exact diagnosis of the sleep disorder in comorbidity and the planning of the intervention could require a more in-depth assessment using objective tools (such as actigraphy and polysomnography).6 Therefore, the management of sleep disorders in children with ASD requires close cooperation between the pediatrician and the child neurologist.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
- Baio J, Wiggins L, Christensen DL, et al. Prevalence of autism spectrum disorder among children aged 8 years - Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2014. MMWR Surveill Summ. 2018;67(6):1–23. doi:10.15585/mmwr.ss6706a1 [CrossRef] PMID:29701730
- Alexeeff SE, Yau V, Qian Y, et al. Medical conditions in the first years of life associated with future diagnosis of ASD in children. J Autism Dev Disord. 2017;47(7):2067–2079. doi:10.1007/s10803-017-3130-4 [CrossRef] PMID:28434058
- Delahaye J, Kovacs E, Sikora D, et al. The relationship between health-related quality of life and sleep problems in children with autism spectrum disorders. Res Autism Spectr Disord. 2014;8(3):292–303. doi:10.1016/j.rasd.2013.12.015 [CrossRef]
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- Moore M, Evans V, Hanvey G, Johnson C. Assessment of sleep in children with autism spectrum disorder. Children (Basel). 2017;4(8):E72. doi:10.3390/children4080072 [CrossRef] PMID:28786962
- Cortesi F, Giannotti F, Ivanenko A, Johnson K. Sleep in children with autistic spectrum disorder. Sleep Med. 2010;11(7):659–664. doi:10.1016/j.sleep.2010.01.010 [CrossRef] PMID:20605110
- Souders MC, Zavodny S, Eriksen W, et al. Sleep in children with autism spectrum disorder. Curr Psychiatry Rep. 2017;19(6):34. doi:10.1007/s11920-017-0782-x [CrossRef] PMID:28502070
- Owens JA, Mindell JA. Pediatric insomnia. Pediatr Clin North Am. 2011;58(3):555–569. doi:10.1016/j.pcl.2011.03.011 [CrossRef] PMID:21600342
- Taira M, Takase M, Sasaki H. Sleep disorder in children with autism. Psychiatry Clin Neurosci. 1998;52(2):182–183. doi:10.1111/j.1440-1819.1998.tb01018.x [CrossRef] PMID:9628139
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- Krakowiak P, Goodlin-Jones B, Hertz-Picciotto I, Croen LA, Hansen RL. Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study. J Sleep Res.2008;17(2):197–206. doi:10.1111/j.1365-2869.2008.00650.x [CrossRef] PMID:18482108
- Köse S, Yılmaz H, Ocakoğlu FT, Özbaran NB. Sleep problems in children with autism spectrum disorder and intellectual disability without autism spectrum disorder. Sleep Med. 2017;40:69–77. doi:10.1016/j.sleep.2017.09.021 [CrossRef] PMID:29221782
- Esbensen AJ, Schwichtenberg AJ. Sleep in neurodevelopmental disorders. Int Rev Res Dev Disabil. 2016;51:153–191. doi:10.1016/bs.irrdd.2016.07.005 [CrossRef] PMID:28503406
- Mazzone L, Postorino V, Siracusano M, Riccioni A, Curatolo P. The relationship between sleep problems, neurobiological alterations, core symptoms of autism spectrum disorder, and psychiatric comorbidities. J Clin Med. 2018;7(5):E102. doi:10.3390/jcm7050102 [CrossRef] PMID:29751511
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- Cohen S, Fulcher BD, Rajaratnam SMW, et al. Sleep patterns predictive of daytime challenging behavior in individuals with low-functioning autism. Autism Res. 2018;11(2):391–403. doi:10.1002/aur.1899PMID:29197172 [CrossRef]
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