Artigo 01

RESEARCH ARTICLE
Effectiveness of non-pharmacological
interventions for insomnia in children with
Autism Spectrum Disorder: A systematic
review and meta-analysis
Sophie Keogh1☯, Christopher Bridle2‡, Niroshan A. Siriwardena2‡, Amulya Nadkarni1,
Despina Laparidou ID2‡, Simon J. Durrant2, Niko Kargas2, Graham R. Law2,
Ffion Curtis ID2☯*
1 Lincolnshire Partnership Foundation Trust, Lincoln, United Kingdom, 2 Lincoln Institute for Health,
University of Lincoln, Lincoln, United Kingdom
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a1111111111 ☯ These authors contributed equally to this work.
a1111111111 ‡ These authors also contributed equally to this work.
* [email protected]
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Abstract
OPEN ACCESS Background

Citation: Keogh S, Bridle C, Siriwardena NA, Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterised
Nadkarni A, Laparidou D, Durrant SJ, et al. (2019)
by behavioural, communication and social impairments. The prevalence of sleep distur-
Effectiveness of non-pharmacological interventions
for insomnia in children with Autism Spectrum bances in children with ASD is 40–80%, with significant effects on quality of life for the chil-
Disorder: A systematic review and meta-analysis. dren and carers.
PLoS ONE 14(8): e0221428. https://doi.org/ This systematic review aimed to synthesise evidence of the effects of behavioural inter-
10.1371/journal.pone.0221428
ventions to improve sleep among children with ASD.
Editor: Jacobus P. van Wouwe, TNO,
NETHERLANDS Methods
Received: June 17, 2019 Databases (MEDLINE, PsycINFO, CINAHL, ScienceDirect, Autism Data, CENTRAL, Clini-
Accepted: August 6, 2019 calTrials.gov and Current Controlled Trials) were searched for published, unpublished and
Published: August 22, 2019 ongoing randomised controlled trials evaluating the effect of non-pharmacological interven-
tions for insomnia in children with autism spectrum conditions.
Copyright: © 2019 Keogh et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which Results
permits unrestricted use, distribution, and
Three studies met the inclusion criteria, one provided actigraphy data, one Children’s Sleep
reproduction in any medium, provided the original
author and source are credited. Habits Questionnaire (CSHQ) data, and one both actigraphy and CSHQ data for use in
meta-analyses. There were significant differences between the behavioural intervention
Data Availability Statement: All relevant data are
within the manuscript and its Supporting and comparison groups (actigraphy data) for total sleep time (24.41 minutes, 95% CI 5.71,
Information files. 43.11, P = 0.01), sleep latency (-18.31 minutes, 95% CI -30.84, -5.77, P = 0.004) and sleep
Funding: The author(s) received no specific efficiency (5.59%, 95% CI 0.87, 10.31, P = 0.02). There was also a favourable intervention
funding for this work. effect evident for the subjective CSHQ data (-4.71, 95% CI -6.70, -2.73, P<0.00001). Risk of
Competing interests: The authors have declared bias was low across several key domains (randomisation, allocation concealment and
that no competing interests exist. reporting), with some studies being unclear due to poor reporting.
PLOS ONE | https://doi.org/10.1371/journal.pone.0221428 August 22, 2019 1 / 13

Non-pharma interventions for insomnia in children with ASD: A systematic review and meta-analysis
Conclusions
There are very few high quality randomised controlled trials in this area. Here we provide ini-
tial synthesised quantitative evidence of the effectiveness of behavioural interventions for
treating sleep problems in children with ASD.
Trial registration
Protocol was registered (CRD42017081784) on the International Prospective Register of
Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO).
Background
Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterised by
behavioural, communication and social impairments [1]. Worldwide it is estimated that 1 in
160 children has an ASD [2]. Disordered sleep is one of the most common reasons parents
seek medical support [3], with 40–80% of children with ASD having sleep difficulties [4].
Behaviours associated with disordered sleep in ASD include difficulty self-settling, frequent
night waking, greater sleep onset latency, early waking and poor sleep efficiency (ratio of total
sleep time to total time spent in bed) [4]. Disordered sleep can exacerbate some of the symp-
toms of ASD, such as over activity, disruptive behaviour, communication difficulties, repetitive
behaviours and social skill deficits, which is not only impairing for the child, but will also
increase family/caregiver stress [5, 6]. There are also lasting effects as adequate quantity and
quality of sleep during childhood years is essential for neuronal development, which deter-
mines long-term trajectories of behaviour, learning, health and wellbeing [7].
In 2017, Cuomo et al. [7] conducted a meta-synthesis of eight reviews examining the effi-
cacy of various sleep interventions, including pharmacologic treatments, alternative therapies
and behavioural interventions, in children with ASD. Two of the included reviews [1, 8]
focused on behavioural interventions in children with ASD, identifying a total of 15 studies.
Overall Cuomo et al. [7] concluded that parent education and behavioural interventions
showed the most promise for the treatment of multiple sleep problem domains. More recently,
Kilpatrick et al. [9] conducted a systematic review of the literature focusing on the efficacy of
parent training incorporated in behavioural sleep interventions for children with ASD and/or
intellectual disabilities. They concluded that the inclusion of parent training within beha-
vioural sleep interventions was considered generally effective, was valued by parents, and 9 of
the 11 studies reported a reduction in sleep problems. These reviews included a broad range of
studies (different research designs, diverse sample populations, a variety of intervention types,
and a range of outcome measures), so the review authors [7, 9] were able to maximize the use
of the evidence available; however, this was also limiting, as it was not possible to then statisti-
cally quantify intervention effects (e.g. a meta-analysis).
Sleep research is a rapidly developing area with emerging evidence indicating that sleep dis-
turbances are not merely consequences of disease, but play important roles in their develop-
ment [10]. Improving sleep outcomes is considered a priority in children with ASD, where
development is already compromised [11]. The evidence for pharmacological interventions
such as melatonin is inconclusive, reporting mixed findings in relation to dose, effectiveness
and side-effects [12]. The National Institute for Health and Care Excellence [13] recommend
that behavioural interventions are first line treatment for insomnia in ASD. Pharmacological

interventions are only to be considered if sleep problems persist despite following the sleep
plan (behavioural intervention), and are still only to be prescribed in conjunction with non-
pharmacological interventions. Importantly, parents consider behavioural interventions as
preferable to, and as effective as, medication [14]. Consequently, there is growing interest in
the development of effective non-pharmacological interventions for treating insomnia. This is
of particular importance in children with ASD and so supports the need to confirm the effec-
tiveness of behavioural interventions in this population.
The aim of this review was to provide an up-to-date synthesis of the available evidence,
focusing on behavioural interventions targeting sleep problems, compared to no intervention,
in children with ASD.
Methods
The inclusion criteria and methods of analysis were specified in advance and documented in a
protocol that was registered (CRD42017081784) on the International Prospective Register of
Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO). This review was reported in
accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis’
(PRISMA) guidelines [15] (S1 PRISMA Checklist).
Eligibility criteria
Studies were considered for inclusion if they were randomised controlled trials (RCTs) of
sleep-based behavioural interventions for children with ASD. In order for a study to be consid-
ered for inclusion the sample would have to be children aged 18 years or under. The review
included studies in which participant eligibility required a pre-existing diagnosis of ASD. Stud-
ies of behavioural interventions targeting sleep compared with concurrent control that
reported relevant sleep outcome measures were eligible. Behavioural interventions were
defined as an intervention which uses behavioural techniques, such as reinforcement to sup-
port the desired behaviour.
Study identification
To identify existing relevant systematic reviews, published, unpublished and ongoing trials,
the following electronic databases were searched from inception to January 2019: MEDLINE,
PsycINFO, CINAHL, ScienceDirect, Web of Science, Autism Data, CENTRAL, ClinicalTrials.
gov and Current Controlled Trials. No restrictions on language were imposed. Database
searching was supplemented with internet searching (e.g. Google Scholar), and forward and
backward citation tracking from systematic reviews and included studies. Key search terms for
database searching included the following:
("Autism spectrum disorder" OR asd OR autism) AND (sleep OR insomnia OR "bedtime resis-
tance" OR dyssomnia) AND (child OR toddler OR infant OR adolescent OR preschool OR
teenage OR pediatric OR paediatric OR childhood)
Search terms used in the MEDLINE search are provided in Supplementary Material: S1
Electronic Search Strategy.
Search results were downloaded to Endnote, and duplicate citations were removed. Two
reviewers independently screened titles and abstracts against the inclusion criteria. Where
studies could not be excluded based on title and abstract, two reviewers independently assessed
full papers for relevance. Any discrepancies were resolved through discussion or, where
required, through involvement of a third reviewer.

Data abstraction
Data were extracted by one reviewer and checked for accuracy by another using a template
that included: (a) study details, for example title, aim, design and type of intervention; (b) par-
ticipant information, for example age, gender, diagnosis, severity, co-morbidities and inclu-
sion/exclusion criteria; (c) groups, for example number randomised, description of
intervention and comparator, delivery, content, frequency, duration and provider; (d) out-
comes, for example primary outcome name, definition, type, how it is measured and reported,
missing data and reasons for missing data.
Risk of bias assessment

Two reviewers independently assessed risk of bias (Cochrane Risk of Bias assessment tool) on
key dimensions including: Random sequence generation, allocation concealment, blinding,
and incomplete outcome data. Each domain was classified as adequate (low risk of bias), inad-
equate (high risk of bias) or unclear (not possible to determine risk of bias). An overall study
risk of bias was not assessed and data for each domain are presented for readers to interpret in
context with review findings. Risk of bias assessment was not used as a reason for exclusion.
Data analysis
All analyses were conducted using Review Manager (RevMan) version 5.3 [16] software for
Windows. All studies reported changes in sleep as a continuous outcome. The primary out-
come was a mean difference in total sleep duration (actigraphy data), which was reported in 3
studies [17]. Secondary outcomes included sleep latency and sleep efficiency (actigraphy data),
and total score from the CSHQ [18]. The summary measure of treatment effect for both pri-
mary and secondary outcomes was the between groups difference in sleep outcomes, expressed
as mean difference (MD).
Random-effects models were used in all meta-analyses, as they are more conservative than
the fixed effects models since, by incorporating within- and between-study variance, the confi-
dence intervals for the summary effect are wider. Statistical heterogeneity was assessed using
the I2 test, which described the percentage of variability among effect estimates beyond that
expected by chance. In cases where heterogeneity was considered to be important (I2 values
�40%), sources of clinical and methodological diversity were explored.
Results
After removal of duplicate citations, the search strategy identified 3,505 distinct citations, of
which 3,453 were excluded during the initial screening phase (Fig 1). For the remaining 52
citations, full text papers were ordered. Three studies met the inclusion criteria [17, 19, 20].
The main reasons for exclusion of full text papers were study design (n = 33), outcome mea-
sures (n = 5), and intervention (n = 11).
Characteristics of included studies

The three included studies [17, 19, 20] were published between 2012 and 2015, see Table 1.
These were conducted in the US [17], Australia [20] and Italy [19]. The three studies rando-
mised 146 participants, with intervention group sample sizes ranging between 18 and 33 par-
ticipants. The mean age of study populations ranged from 6.3 years [17] to 10.3 years [20].
Participants within the included studies were all required to have a diagnosis of ASD. In
two [17, 19] of the three studies, diagnosis was based on clinical evaluation using the Diagnos-
tic Statistical Manual–Fourth Edition-TR (DSM-IV-TR, American Psychiatric Association

Fig 1. Flow diagram of study selection [15].

https://doi.org/10.1371/journal.pone.0221428.g001
2000) and confirmed by the Autistic Diagnostic Interview–Revised (ADI-R) and/or the
Autism Diagnostic Observation Schedule–generic (ADOS-G). In the third study, a clinician
diagnosis of an ASD was confirmed by parents of the participants [20].
To identify sleep problems in participating children, two studies [17, 19] used parental
report of sleep difficulties, including consideration of sleep onset latency, wake after sleep
onset or night-time awakenings. The third study required participants to have sleep onset dis-
order, limit setting disorder, delayed sleep phase or insomnia as defined by the American
Academy of Sleep Medicine [20].
Common participant exclusion criteria in the individual studies included current receipt of
pharmacological treatments, psychotherapy or a behavioural intervention, sleep disordered
breathing [19], Periodic Limb Movement [19], serious medical or mental health conditions
[20], and sleep apnea [17, 20].
Delivery of behavioural interventions varied across the different studies. Adkins et al. [17]
provided an education pamphlet for parents to read and follow without further instruction
from the study staff. Experienced clinical psychologists delivered four-weekly 50-minute face-
to-face CBT sessions in the Cortesi et al. [19] study. This was delivered in an outpatient univer-
sity clinic and completion was defined as completion of the baseline session and at least two
treatment sessions. Papadopoulos et al. [20] used two face-to-face sleep consultations and a fol-
low-up phone call with a trained clinician, each two weeks apart, to deliver their intervention.
This study also provided the most details in relation to sleep disorders, definitions and

Table 1. Study characteristics.

Study (location) Sample size, age Intervention, frequency, duration and components. Comparison Baseline data: mean
(years), sex ±SD, end-time
point
1
Cortesi et al., Intervention: n Four-arm study. Placebo provided during fortnightly 15 minute Actigraphy2 TST
(2012) 33 Baseline evaluation and 4-weekly 50 minute CBT meetings to match melatonin arm of study. Intervention: 408.08
Rome [19] Age: 7.1 (0.7) sessions over 12 weeks to include a sleep focused (49.03)
83% male multifactorial intervention with cognitive, Control: 413.00
Control: n 32 behavioural and educational components. Session 1: (45.13)
Age 6.3 (1.2) information giving about sleep (nature, function and Sleep onset delay
84% male regulation), Session 2: parents were instructed to Intervention: 76.34
create consistent sleep schedule, session 3: reviewing (31.70)
instructions and identifying individual difficulties Control: 78.20
and implementation of methods to replace any (33.83)
remaining maladaptive behaviours with more Sleep efficiency %
appropriate sleep habits, session 4: reviewed Intervention: 71.37
instructions and information on prevention of (4.77)
insomnia relapse. Additionally, parents attended Control: 71.13
twice-monthly individually tailored CBT sessions. (4.99)
The focus of maintenance sessions was on CSHQ
consolidating treatment strategies learned during Intervention: 64.48
initial therapy and developing methods for coping (5.48)
for residual insomnia. Control: 64.20
(4.85),
12 weeks
Adkins et al., Total age 6.4 ±6 Sleep education pamphlet, self-administered, (2 No pamphlet. Control group to receive pamphlet Actigraphy2 TST
(2012) 2.6 weeks) to include (1) providing a comfortable sleep after the study was completed. Intervention: 465.7
North America Intervention: n setting; (2) establishing regular bedtime habits;(3) (66.3)
[17] 18 keeping a regular schedule; (4) teaching your child to Control: 461.4
age fall asleep alone; (5) avoiding naps (in children who (42.4)
55% male have outgrown the need for a daytime nap); and (6) Sleep onset delay
Control: n 18 encouraging daytime activities that promote a better Intervention: 56.7
Age sleep/wake schedule. (27.1)
78% male Control: 52.1 (25.1)
Sleep efficiency %
Intervention: 75.5
(6.1)
Control: 76.8 (6.0),
2 weeks
Papadopoulos Intervention: n Two face-to-face sleep consultations and follow-up Usual care (for ADHD): Paediatrician apt CSHQ
et al., (2015) 28 phone call with clinician 2 weeks apart. An typically every 6 months to check height, weight, Intervention 56.7
Australia [20] Age 10.3 (1.7) assessment of child’s sleep problem, discussion of and blood pressure and to re-issue a prescription (6.6)
85.7% male parental goals, and psychoeducation about normal medication and/or brief behavioural strategies Control 57.7 (9.4),
Control: n 33 sleep, sleep cycles, and sleep hygiene strategies. which do not routinely include sleep strategies. 3 months
Age 9.8 (2.0) During this consultation, a tailored behavioural sleep
90.9% male management plan was formulated. The second
consultation and follow-up phone call were used to
review the sleep diary, reinforce strategies, and
troubleshoot any problems. Information sheets
addressing normal sleep, common sleep problems,
and strategies for managing specific problems were
provided.
1
four-arm trial: combination therapy group, melatonin group, CBT group and placebo group.
2
Actigraphy TST: total sleep time
https://doi.org/10.1371/journal.pone.0221428.t001
examples of behavioural interventions (e.g. sleep onset association disorder, child associates
falling asleep with a certain objector person which would be addressed by Parental presence at
sleep time being managed with adult fading/graduated extinction).
All studies were two-arm design RCTs (intervention vs control) with the exception of Cor-
tesi et al. [19], who investigated the relative and combined effects of melatonin and CBT,

Fig 2. Actigraphy total sleep time (minutes) in children with ASD.

compared to a placebo control (four-arm). Primary outcomes for the included studies were
sleep measures; actigraphy data [17], CSHQ scores [20] or both actigraphy data and CSHQ
scores [19].
Of the 28 participants in the intervention group of the Papadopoulos et al. [20] study, 26
were taking medications such as Ritalin, Concerta, or Clonidine. In the control group, 27 of
the 33 participants were taking medications: Ritalin, Concerta, and Atomexetine. Five children
in the intervention group (n = 18) in the Adkins et al. [17] study were taking psychotropic
medications, three were taking melatonin and two stimulants. Within the control group
(n = 18), nine were taking psychotropic medications, three melatonin and two stimulants. All
children in the Cortesi et al. [19] study were drug free for at least six months and no children
receiving psychotherapy or behavioural interventions were enrolled in the study.
Of the two studies [17, 19] that used actigraphy devices to measure sleep outcomes, data for
total sleep time measured in minutes (Fig 2), sleep onset latency (time from lights out to mea-
sured first sleep onset) (Fig 3), and sleep efficiency (ratio of total sleep time to total time in
bed) (Fig 4) were available for statistical analysis. Adkins et al. [17] collected actigraphy data
via AW Spectrum Acti-watch devices (Phillips Respironics, Bend, OR) for two weeks following
a 2-week pamphlet intervention period. Cortesi et al. [19] monitored each child with an acti-
graphy device in the zero crossing mode from the Ambulatory Monitoring Inc. (Ardsley, NY,
USA) for a minimum of seven nights following 12 weeks of CBT. Actigraphy devices were
used in conjunction with parent report sleep diaries in both of the studies. Adkins et al. [17]
used the devices to confirm parent report and Cortesi et al. [19] recommended parents kept
diaries to enable editing of actigraphy data for potential artefacts and failures.
Two studies [19, 20] reported outcome data using the CSHQ. This is a standardised ques-
tionnaire designed for use in children. It includes 45 items and is rated retrospectively over the
previous week to screen for common sleep problems in key areas such as child bedtime, sleep
behaviour and night time waking. Both studies reported a total sleep disturbance score for the
questionnaire, which was used for the pooled data synthesis (Fig 5). A total score of 41 is con-
sidered the optimal clinical cut-off for sleep disturbance [18].
Meta-analysis of two studies [17, 19] demonstrated a statistically significant increase in total
sleep time following behavioural sleep interventions (Fig 2, 24.41, 95% CI 5.71, 43.11,
P = 0.01). There was no indication of statistical heterogeneity among the studies reporting
total sleep time (I2 = 0%). The synthesised data from these two studies also demonstrated a sig-
nificant between groups mean difference (-18.31, 95% CI -30.84, -5.77, P = 0.004) in sleep
onset latency, favouring the intervention group (Fig 3). When sleep efficiency (%) data from
Fig 3. Actigraphy sleep onset latency (minutes) in children with ASD.


Fig 4. Actigraphy sleep efficiency (%) in children with ASD.

the two studies were synthesised, a statistically significant effect was observed on sleep efficiency
following a behavioural sleep intervention (5.59, 95% CI 0.87, 10.31, P = 0.02); however, sub-
stantial heterogeneity (Chi2 = 3.92, df = 1, P = value = 0.05; I2 = 75%) was evident (Fig 4). Data
are presented here as a sensitivity analysis was not possible with only two studies included. The
final meta-analysis synthesising CSHQ data from two studies [19, 20] demonstrated a statisti-
cally significant behavioural intervention effect when compared to control (-4.71, 95% CI -6.70,
-2.73, P<0.00001), with no evidence of statistical heterogeneity (I2 = 0%) (Fig 5).
Risk of bias
Randomisation processes were well described in all studies and as such random sequence gen-
eration risk of bias was low for all studies (see Table 2). Allocation concealment was considered
to be of a low risk of bias for two studies [19, 20] and unclear in the remaining study [17] due
to absence of reporting. It was not possible to blind participants to which arm of the interven-
tion they had been randomised to, hence, all studies were considered to be high risk of bias for
the category ‘blinding of participants and personnel’. The assessment of risk of bias for the
domain ‘blinding of outcome assessment’ is presented separately for parent-reported CSHQ
and the more objective actigraphy measure. The actigraphy data from the Adkins et al. [17]
study was uploaded to a database for centralized scoring, by a single individual who had no
contact with participants. There was no information available for the Cortesi et al. [19] study.
It was considered that there could be a higher risk of bias for the CSHQ, as parents were the
first line assessors, subjectively scoring their children’s sleep behaviours. Again data processing
procedures were not described. The risk of bias for ‘Incomplete outcome data’ was considered
high in the Papadopoulos et al. [20] study, with only 75% of intervention group and 73% of
usual care group providing follow up data. All studies were considered to have low risk of bias
for ‘selective outcome reporting’ as all measures described were reported in the results section.
Discussion
The aim of this review was to systematically review and quantify the effects of behavioural
interventions targeting sleep problems in children with ASD. Three studies evaluating the
effect of behavioural interventions on sleep outcomes in children with ASD were retrieved.
One of the studies [17] provided actigraphy data, one total scores for CSHQs [20], and one
study [19] reported both actigraphy and CSHQ data.
Synthesised actigraphy data showed a statistically significant effect of behavioural interven-
tions compared to control on children’s total sleep time (24 minutes), sleep onset latency (-18
Fig 5. Children’s sleep habits questionnaire total score.


Table 2. Risk of bias.

Study ID Random Allocation Blinding of Blinding of outcome Blinding of Incomplete Selective
sequence concealment participants and assessment outcome outcome data outcome
generation personnel (Actigraphy) assessment reporting
(CSHQ)
Papadopoulos low low high - high high low
2015 [20]
Cortesi 2012 [19] low low high Unclear high low low
Adkins 2012 [17] low unclear high Low - low low
https://doi.org/10.1371/journal.pone.0221428.t002
minutes) and sleep efficiency (5.5%). Substantial heterogeneity was evident in the pooled anal-
ysis of the sleep efficiency data; the reason for this was not clear, so data were still presented.
The final meta-analysis combining CSHQ total scores from two studies were in agreement
with the actigraphy results, demonstrating a significant intervention effect (-4.7 CSHQ score)
when compared to non-intervention comparison groups.
Strengths and weaknesses of study

To inform the methodology, selection, evaluation and syntheses of relevant evidence, this
study adhered to the PRISMA reporting guidelines and a rigorous pre-specified protocol
(PROSPERO), thus, limiting the potential for bias. Comprehensive searching of multiple elec-
tronic databases for published and unpublished work, bibliography scanning and contacting
authors identified only three published studies [17, 19, 20], all of which had relatively small
sample sizes. Despite this, data were available to conduct the first meta-analysis, synthesising
the effects of behavioural interventions targeting sleep problems in children with ASD.
A potential weakness of this review was the absence of data from unpublished studies,
which could increase the potential risk of publication bias. Due to the small number of studies
included within this review, it was not possible to conduct a funnel plot. However, publication
bias was deemed unlikely, as two of the three included studies did not report significant effects
for the outcomes of interest in this review.
Evidence from individual studies in the current review was synthesised despite variation in
intervention delivery (face to face, pamphlet) and duration (two to 12 weeks). There are only a
limited number of studies in the area and the decision to combine data from the included stud-
ies was based on previous research that observed similar positive treatment outcomes from dif-
ferent types of interventions (group vs individual interventions and those ranging from two to
five weeks) [9].
Both objective and subjective outcome measures were included within this review, as they
provide complementary information [21]. There was some variation in placement of actigra-
phy devices in the Adkins et al. [17] study, where wrist placement was tolerated by 27 (75%) of
the children, whereas nine (25%) children required the shoulder placement. There were no dif-
ferences reported for the actigraphy data in children who wore actigraphy devices on the wrist
or shoulder [17]. Actigraphy devices are now commonly used in sleep research [22] for the
assessment of various sleep parameters, including total sleep duration, sleep onset latency and
sleep efficiency. Future work should explore variation in actigraphy device placement in chil-
dren where wrist placement may not always be well tolerated.
Subjective measures, such as the CSHQ, are important as they reflect the subjective percep-
tion, which is arguably more ‘ecologically’ sound and is crucial in the management process of
the disorder [21]. The CSHQ demonstrates adequate internal consistency and acceptable test-
retest reliability in typically developing children [18] and is currently the most widely used
standardized sleep assessment tool for children with ASD [22].

Discussion of findings
The interventions in the included studies aimed to educate parents with strategies to improve
sleep behaviours in their children, which is considered the best evidence-based practice in this
population [23]. The depth of descriptions of the interventions included within the primary
papers varied, with Papadopoulos et al. [20] providing the most information. Components of
the behavioural intervention described by Papadopoulos et al. [20], such as emphasizing a
calming bedtime using relaxation training, would be considered effective for many forms of
insomnia, including those related to core deficits of ASD [24]. Cortesi et al. [19] provided an
outline of each of the sessions. The Adkins et al. [17] study reported six areas relevant to pro-
moting sleep among children with ASD provided within the pamphlet in the Adkins et al. [17]
study. It was, however, clear from the information available that the interventions were all
quite different from one another with regards to content and ‘dose’, which should be explored
further.
The summary effect for total sleep duration and sleep onset delay demonstrated statistically
significant differences favouring the intervention groups. Only one [19] of the included origi-
nal studies reported a significant effect post-intervention. This study had the largest sample
size and was the only included study in which children were free from medication. Despite
children in the two smaller studies [17, 20] being on one or more medications, a promising
treatment effect was still observed post intervention. In addition to establishing the effective-
ness of behavioural interventions for insomnia in a drug free population, future research
should explore this in the presence of medications, as it is estimated that 30%–65% of children
with ASD use at least one psychotropic medication [25].
Both of the included actigraphy studies [17, 19] reported a significant intervention effect for
sleep efficiency. The improvement in the original pamphlet study [17] was only a two percent-
age point absolute change, from 75% to 77%, which is unlikely to be clinically meaningful.
This was larger in the Cortesi et al. [19] study (8%) and the between groups difference pre-
sented here was 5.5%, which may be clinically meaningful for some participants. Different
delivery formats warrant further investigation as, in agreement with Kilpatrick [9], this review
indicates that both face-to-face CBT and a more simple information pamphlet are effective in
this population. The individual point estimate from the meta-analysis presented here indicated
a positive post intervention effect for the Adkins et al. [17] study, which was only a two week
self-administered pamphlet.
The CSHQ total score between-groups difference favoured the intervention and was statis-
tically significant. It is difficult to determine if this is clinically meaningful, as the CSHQ was
developed to classify sleep (e.g. a total score of 41 is considered the optimal clinical cut-off for
sleep disturbance; [18]) and as such should be used in conjunction with other sleep measures
when evaluating interventions.
Risk of bias was low across several key domains (randomisation, allocation concealment
and reporting) with some studies being unclear due to poor reporting. There were some
domains where it was difficult to eliminate potential for bias due to study design; for example,
blinding of participants and personnel. Whilst it is unlikely this would directly influence the
children’s actigraphy data, risk of bias may influence parents’ reporting for the CSHQs and
diaries that were kept in conjunction with the actigraphy data. In addition to this, parents
would not have been blinded to outcome assessment when completing CSHQs.
Previous reviews [1, 7–9] have included a broader range of studies to provide a comprehen-
sive overview. However, by including studies with different designs, intervention types and
participant characteristics, it has not been possible to draw definitive conclusions quantifying
intervention effects. A recent review [26] suggests a transdiagnostic treatment approach across

different developmental orders may be effective; however, they conclude more research is
needed prior to any recommendations being made. In comparison, this review had a narrow
focus to begin refining the evidence in this area by statistically quantifying the effects of beha-
vioural interventions in children with ASD. Future research should also consider focusing on
children with ASD and not grouping them with other ‘developmental disorders’ as previous
studies (blindness, Down syndrome in [27]) have done, as children with different conditions
would likely respond differently to behavioural interventions. This is particularly relevant
when considering sleep problem behaviours in children with ASD.
Implications
The evidence presented in the current review will be useful for clinical practice in the manage-
ment of sleep problems in children with ASD, enabling clinicians and families to make
informed choices. Despite behavioural interventions being the recommended first line treat-
ment, and sleep medication being associated with lower quality-of-life scales and more chal-
lenging daytime behaviours, pharmacological prescribing is common with many children
being prescribed more than one type of sleep medication [25]. Behavioural interventions are
advantageous as they are preferred by parents and have positive effects on sleep difficulties in
ASD without the risk of adverse effects associated with pharmacological approaches [12].
Behavioural interventions also have the additional advantage that they can be delivered for
long periods of time if required, and in case of relapse, without concerns about untoward
effects associated with long term use of medication.
Here we provide preliminary quantitative evidence of the effectiveness of behavioural inter-
ventions for treating sleep problems in children with ASD. Future research should explore the
effect of behavioural interventions alone and in combination with other medications in chil-
dren with ASD.
In preparing this review it was evident that interventions targeting sleep problems is a rap-
idly evolving area of research. This review has presented all available evidence to date, how-
ever, the authors are aware of at least one ongoing study with a planned completion date of
2023; Telehealth Delivery of Treatment for Sleep Disturbances in Young Children With
Autism Spectrum Disorder [28].
Supporting information
S1 PRISMA Checklist.
(DOC)
S1 Electronic Search Strategy.
(DOCX)
Acknowledgments
We like to acknowledge the support of Tracy McCranor, Clinical Research Manager from Lin-
colnshire Partnership NHS Foundation Trust who had a role in the early development of the
protocol for this systematic review.
Author Contributions
Conceptualization: Christopher Bridle, Niroshan A. Siriwardena, Amulya Nadkarni, Graham
R. Law.
Investigation: Sophie Keogh, Despina Laparidou, Ffion Curtis.

Project administration: Ffion Curtis.

Supervision: Christopher Bridle, Niroshan A. Siriwardena, Amulya Nadkarni.
Writing – original draft: Sophie Keogh, Ffion Curtis.
Writing – review & editing: Christopher Bridle, Niroshan A. Siriwardena, Amulya Nadkarni,
Despina Laparidou, Simon J. Durrant, Niko Kargas, Graham R. Law.
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RESEARCH ARTICLE

OPEN ACCESS Background

PLOS ONE | https://doi.org/10.1371/journal.pone.0221428 August 22, 2019 1 / 13

PLOS ONE | https://doi.org/10.1371/journal.pone.0221428 August 22, 2019 2 / 13

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Risk of bias assessment

Characteristics of included studies

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Fig 1. Flow diagram of study selection [15].

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Table 1. Study characteristics.

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Fig 2. Actigraphy total sleep time (minutes) in children with ASD.

Fig 3. Actigraphy sleep onset latency (minutes) in children with ASD.

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Fig 4. Actigraphy sleep efficiency (%) in children with ASD.

Fig 5. Children’s sleep habits questionnaire total score.

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Table 2. Risk of bias.

Strengths and weaknesses of study

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Project administration: Ffion Curtis.

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PLOS ONE | https://doi.org/10.1371/journal.pone.0221428 August 22, 2019 13 / 13

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