A Practice Pathway for the Treatment of Night Wakings in Children with Autism Spectrum Disorder

Approximately 1 in 44 children have autism spectrum disorder (ASD), defined by diagnostic criteria that include deficits in social communication and social interaction, and restricted or repetitive patterns of behavior, interests, or activities (Maenner et al., 2021). Sleep problems commonly co-occur in this population; indeed, sleep problems are estimated to be more than twice as common in young children ages 2–5 years with ASD than in the general population (Reynolds et al., 2019), and they often persist into adolescence (Goldman et al., 2012). Approximately 50–80% of parents of children with ASD report sleep problems in their child (Couturier et al., 2005; Goldman et al., 2012; Krakowiak et al., 2008), including various types of insomnia, such as difficulty falling asleep, bedtime resistance, prolonged night wakings, and short sleep duration (Richdale & Schrek, 2009; Williams et al., 2004).

Sleep problems in children with ASD are associated with hyperactive/impulsive behavior, disruptive behavior and other daytime behavior problems. Night wakings in particular show associations with physical aggression, irritability, and hyperactivity (Mazurek & Sohl, 2016). Night wakings and sleep onset delay contribute to short sleep duration, which is associated with poorer adaptive functioning in daily living skills, social skills, motor development; and restricted and repetitive behaviors (Taylor et al., 2012; Veatch et al., 2017). Health-related quality of life is also affected in children with ASD and short sleep duration (Delahaye et al., 2014). Furthermore, bidirectional relationships of disordered sleep with immune dysregulation make children at greater risk for other physical and neuropsychiatric problems (Iranzo, 2020; Louveau et al., 2015; Winkelman & Lecea, 2020; Yin et al., 2021; Zielinski & Gibbons, 2022). Beyond the child’s own health, consistent sleep problems contribute to maternal stress and poorer maternal mental health (Hodge et al., 2013). Fortunately, treatment of sleep problems in children with ASD, using behavioral or pharmacologic approaches, results in improvements in child behavior and family functioning (Malow et al., 2012, 2014).

To address the multifaceted problem of sleep disturbance and related impairments, the joint Autism Speaks Autism Treatment Network and Autism Intervention Research Network on Physical Health (ATN/AIR-P) published a practice pathway for the identification, evaluation, and management of insomnia in children with ASD (Malow et al., 2012). This practice pathway was based on expert consensus with the goal of capturing best practices for an overarching approach to insomnia by a general pediatrician, primary care provider, or autism medical specialist, and included a systematic literature review and grading of evidence. Key points of the practice pathway included (a) screening the child for insomnia using a few targeted questions related to key sleep concerns (e.g., sleep onset delay, co-sleeping, sleep duration, night wakings); (b) identifying and managing medical contributors that can affect sleep (e.g., obstructive sleep apnea, gastroesophageal reflux, epileptic seizures, atopic disease such as asthma and eczema), (c) providing educational/behavioral interventions, and (d) close follow-up, with institution of medications or referral to a sleep specialist for persistent sleep problems. The practice pathway was designed to be broad and cover a variety of sleep problems.

Network providers and parents noted that the 2012 pathway mainly addressed difficulties with sleep onset. The separate issue of night wakings remains challenging and continues to have clinical significance. Even after controlling for the effects of age and sex, night wakings have shown a strong association with daytime behavioral problems (Mazurek & Sohl, 2016). The prevalence of occasional or frequent night wakings in an ATN-related sample was approximately 50% (Katz et al, 2018). There are several reasons for emphasizing night wakings. Night wakings may be reflective of specific medical problems, such as obstructive sleep apnea, which wakes children from sleep to promote a resumption of breathing, poorly controlled asthma or atopic disease, all of which can result in sleep disruption. Indeed, a wide range of major medical conditions such as gastroesophageal reflux (GERD), constipation, restless leg syndrome, or seizures can be associated with night wakings. Finally, although educational/behavioral approaches and pharmacologic intervention are often effective in addressing sleep onset delay, bedtime resistance, and co-sleeping (when reported as problematic by the parent or caregiver), in our clinical experience the sleep concern of night wakings is often refractory to treatment with educational/behavioral approaches and/or pharmacologic intervention. Therefore, the ATN/AIR-P Sleep Committee reconvened to update the 2012 practice pathway for insomnia, with an emphasis on night wakings. In this review, the committee examined the definition of night wakings including number, duration and impacts on children, families and caregivers. The committee recognized that a working definition for night wakings would improve differential diagnosis and evaluation of clinical interventions.

Across the 76 articles reviewed, there was no consistent definition for night wakings. Most articles (63/76) relied upon parent reported measures to assess night wakings..About one-third of the reports (27/76) included actigraphy. Polysomnography was less frequently used (10/76)., or retrospective clinical observation by chart review of parent reported sleep duration or completed sleep questionaires. Within the articles, several sleep disturbances were reported that the committee felt qualified as night wakings. These included nighttime or early morning wakings by subjective parent report, as well as decreased sleep efficiency, sleep fragmentation, and increased wake after sleep onset (WASO) as measured by polysomnography (PSG).

The 76 studies were placed into one or more of five broad categories based on the focus of the article: 1) frequency of night wakings, 2) frequency of night waking in children with ASD vs. children without ASD, 3) evaluation of tools used to identify night wakings, 4) other factors or conditions associated with night wakings, and 5) treatment/intervention for night wakings. Articles that addressed multiple domains were repeated in all relevant categories.

The vast majority of the articles for this review indicated that children with autism have more frequent or longer night wakings than their neurotypically developing peers. Given the prevalence of sleep problems in children with autism and the significant impact that lack of sleep has on child outcomes, there is alarge need for clinical guidelines to manage sleep disturbances in this population. The Sleep Committee of the ATN / AIR-P set out to update the existing practice pathway on insomnia and autism, as the original version of this practice pathway dealt primarily with sleep onset difficulties. The goal of this article is to provide more specific recommendations on night wakings, a frequent sleep problem within the broader diagnosis of insomnia, i.e., the difficulty to initiate or maintain sleep.

This systematic literature review identified 31 articles that were focused specifically on the identification or treatment of night wakings in individuals diagnosed with ASD, consisting mostly of case reports, small case series, or observational studies. There were few randomized controlled trials found in the published literature addressing night wakings in people with ASD. Due to a lack of randomized controlled trials and small sample sizes, the majority of evidence in available treatment studies was Low or Very Low (23/26) based on GRADE guidelines (Frazier et al., 2017). The paucity of data, especially those stemming from high quality research, in this area was surprising given how prevalent the problem appears.

A further limitation of the studies we reviewed was the apparent lack of a consistent definition for night wakings. A clear and consistent definition of night wakings is not currently available in the literature. The working definition of pathogenic night wakings is based on multiple sources including the ICSD-3 diagnostic criteria for insomnia, definition of an abnormal wake after sleep onset (WASO) from the American Academy of Sleep Medicine Manual for the Scoring of Sleep and Associated Events (Berry et al., 2020). It is also differentiated from physiologic arousals that occur at the end of a sleep cycle and based on available literature about the effects of night wakings on children’s sleep and daytime functioning and the effect on parents and caregivers. Based on our review of the literature, we propose a working definition of “night wakings” to be a waking of 30 min or more following sleep onset, or frequent, greater than 1 per night, shorter night wakings after sleep onset that significantly disrupt the child or their family / caregiver(s). Given the subjective data collected by parental survey and sleep diaries we are unable to clearly define the minimal time necessitated to qualify as a shorter night wakening. Night wakings are noted to be full episodes of arousal, confirmed by polysomnography when available, and exclude parasomnias including but not limited confusional arousals and night terrors. Based on this working definition, we compiled the available literature to update the 2012 practice parameter from this committee as well as to guide our recommendations for further research. This working definition represents a first step in understanding the issue so that we can properly identify the occurrence of night wakings, calculate incidence at different ages, evaluate prevalence accurately, and develop and evaluate efficacious treatment options. Future large population-based samples will be necessary to fully assess the issue. We acknowledge that future modifications to this working definition may be necessary based on future work, which may advance clinical guidance and practice.

With respect to the methods employed to evaluate sleep, objective measures were lacking in most of the studies we reviewed. Notably, objective data gathered via polysomnography and actigraphy did not necessarily validate the subjective data collected from parental reports and validated sleep surveys. Many of the articles reviewed here utilized parent or caregiver reports. Reliance upon parent report of sleep disturbances has been found in both typically developing and atypically developing children to overestimate sleep problems. On the other hand, parental reports are critical to our ability to evaluate and treat sleep disturbances in children; indeed, best practices dictate that caregiver input on child symptoms or problems should be actively sought. The difference between parental report and objective data may represent misperceptions of parents but it may also reflect a higher degree of impact on parental sleep disruption caused by the perception of a higher level of intervention necessary when addressing the night wakings in a child with ASD. The need for a more involved response (e.g., a longer period of wakefulness of the parent while trying to assist the child in returning to sleep) may increase awareness of night wakings by parents who have to intervene. Thus, the impact of night waking may have a more dramatic effect on family and parental function when a greater degree of parental intervention is involved even if the frequency and duration of the actual waking is not different. Conversely, parents of children with ASD may be addressing more worrisome or difficult to manage behaviors or medical issues, leading them to underreport sleep disturbance as it might represent a secondary concern when compared with behavioral or medical issues.

As suggested by the prior practice pathway, we recommend that all children with ASD be screened for sleep problems at their annual visit with their primary provider or more frequently if there are reports of increased difficulty with typical daily activities or academic function. Parents may not necessarily discuss sleep problems during their limited time with a physician or other provider, or the sleep issues may get lower priority compared to other concerns. For these reasons, it is important for providers to query the caregiver for any sleep concerns. Furthermore, given what is known about the impact of night wakings on daytime functioning, we recommend that screening used to identify sleep problems should include queries specific to night wakings. Only four articles since the initial practice pathway addressed tools for screening with sleep questionnaires (CSHQ, CGI, Family Inventory on Sleep Habits), actigraphy, and video-somnography. Questionnaires are the most widely available tool to most clinicians outside of a sleep center, but there are no data indicating how frequently these tools are utilized in routine office visits for children with ASD. Actigraphy is a widely accessible tool and often utilized in adult sleep clinics, but has limitations in its role for identification of night wakings in children with ASD (Sitnick et al., 2008), and the gold standard of polysomnography with video is expensive and not readily available. There is still a need to encourage clinicians and families to discuss sleep problems in the clinical setting so that they can be managed.

The prior practice pathway also emphasized identifying coexisting medical conditions that can contribute to sleep problems. The prior practice pathway also recommended behavioral therapies as a first line approach. Both of these principles are also highlighted in a recent American Academy of Neurology guideline (Williams Buckley et al., 2020). Similar to the articles reviewed from the prior practice pathway on insomnia for ASD, the more recent articles we reviewed provided some evidence that medications may be efficacious in managing night wakings. However, because the findings were inconsistent and sample sizes were often limited, additional information is needed in order to understand the utility of a pharmacological approach to addressing night wakings in this population.

Further research in this area should focus on two main goals:1) better identification of night wakings in larger population studies and 2) evidence-based standards for educational/behavioral and/or pharmacologic interventions to treat night wakings in children with ASD.

Future research needs to define normative values and provide clear descriptors of how night wakings were evaluated in upcoming clinical studies. Objectively measured sleep duration and continuity is currently limited to actigraphy at home which is the less reliable, but most accessible, objective measure for measuring wake after sleep onset in comparison to polysomnography. Video polysomnography can be reliably used to measure night wakings but is currently limited to in-lab polysomnography which is expensive and takes the child out of their typical sleep environment and therefore may not accurately reflect sleep disturbances occurring at home (Penzel et al., 2018). The advent of newly available in-home monitoring with video-time lapse, permitting summary data from sleep patterns at home, may be a new avenue for monitoring and quantifiably identifying sleep disruption as well as assessing efficacy of intervention. Wearable technology for monitoring sleep parameters is becoming more sophisticated and user friendly and warrants further evaluation for efficacy especially with more objective longer-term monitoring. The utility of these monitoring devices is as yet unknown and may be considered in future studies, though data privacy limitations will need to be closely considered.

The identification of other health conditions affecting sleep highlights the need for physicians and providers to do a comprehensive evaluation of the child with sleep disturbance. Since children with decreased intellectual functioning have increased reports of night waking, it also suggests that the medical team and caregiver need to be vigilant about other potential health conditions causing sleep disturbance in a child who may not be able to communicate comparably to neuro-typical peers.

A limitation of the studies reviewed is that most were deemed low or very low on the GRADE system, with only three studies deemed of moderate quality. While the treatment trials reviewed were of low to moderate quality, they do provide some guidance. Randomized controlled trials of medications in children with ASD and insomnia are challenging due to concerns about adverse effects, cost of large studies, need for a reliable and valid outcome measure, and the potential complications of co-occurring medical conditions such as epilepsy, which may be treated with medications that may disrupt sleep. The 2012 Practice Parameter identified the role of melatonin and there is also literature that supports decreased melatonin in children with ASD as compared to their age-matched peers. The literature we reviewed identified similar findings and that extended-release melatonin showed a small to medium effect in the treatment of night wakings for children with ASD. Based on this evidence we included extended-release melatonin as part of the practice parameter. The availability of this formulation of melatonin in tablet form will limit usage in much of this population. Health care provides will need to specifically determine whether a child can swallow tablets. In patients who cannot swallow tablets, health care providers and families may consider the assistance of behavioral therapists, speech/language pathologists, and/or occupational therapists to help promote tablet swallowing. The bulk of the literature suggests the safety and efficacy of melatonin along with recommendations for behavioral and environmental interventions. There was insufficient evidence in the literature to evaluate the use of other interventions or devices (for example, medical safety beds) to address night wakings. However, children with autism may have such profound sleep disturbances so as to compel clinicians to prescribe other sleep medications without evidence-based recommendations. Analysis of existing data may be a starting point in understanding the benefits of medications on sleep since many children with autism already take medications. For example, medications such as clonidine, an alpha agonist sometimes used to treat co-occurring ADHD, may have the dual benefit of treating sleep problems. Untangling these relationships is complex, given that these medications may have variable effects on sleep and sleep architecture. A further consideration in understanding the therapeutic role of medications such as melatonin in addressing sleep disturbances in children with ASD is the timing and dosing amount. There is emerging evidence to suggest that administering a small doe of melatonin several hours prior to bedtime can be beneficial for sleep; however, based on our review of the literature, we felt there was insufficient evidence to support a conclusion about the efficacy of various dose administration strategies and timing.

The 2012 practice pathway for evaluation and treatment of insomnia in children with ASD is still relevant and continues to be an effective tool for clinicians. The update proposed here provides and estimate of the prevalence of night wakings in youth with ASD and the effects on daytime functioning warrants further study. A clear, universally applied definition of night wakings in future publications is needed. Our working definition is intended to serve as a jumping off point for this work. We define night wakings here as “A waking of 30 min or more following sleep onset, or frequent shorter night wakings after sleep onset that significantly disrupt the child or their family / caregiver.” The etiology of the night wakings may be multi-factorial and this fact may contribute to the difficulty in quantifying these symptoms in children with ASD. We present these data as a tool for practitioners to identify and treat insomnia in children with ASD and to emphasize that further research is necessary.