Sleep disturbances after pediatric traumatic brain injury: a systematic review of prevalence, risk factors, and association with recovery

Abstract

Study Objectives

Sleep is vital for brain development and healing after injury, placing children with sleep-wake disturbances (SWD) after traumatic brain injury (TBI) at risk for worse outcomes. We conducted a systematic review to quantify SWD after pediatric TBI including prevalence, phenotypes, and risk factors. We also evaluated interventions for SWD and the association between SWD and other posttraumatic outcomes.

Methods

Systematic searches were conducted in MEDLINE, PsychINFO, and reference lists for English language articles published from 1999 to 2019 evaluating sleep or fatigue in children hospitalized for mild complicated, moderate, or severe TBI. Two independent reviewers assessed eligibility, extracted data, and assessed risk of bias using the Newcastle–Ottowa Score for observational studies.

Results

Among 966 articles identified in the search, 126 full-text articles were reviewed, and 24 studies were included (11 prospective, 9 cross-sectional, and 4 case studies). Marked heterogeneity was found in study populations, measures defining SWD, and time from injury to evaluation. Studies showed at least 20% of children with TBI had trouble falling or staying asleep, fatigue, daytime sleepiness, and nightmares. SWD are negatively correlated with posttraumatic cognitive, behavioral, and quality of life outcomes. No comparative intervention studies were identified. The risk of bias was moderate–high for all studies often related to lack of validated or objective SWD measures and small sample size. Heterogeneity precluded meta-analyses.

Conclusions

SWD are important morbidities after pediatric TBI, though current data are limited. SWD have implications for TBI recovery and may represent a modifiable target for improving outcomes after pediatric TBI.

pediatric, brain injury, sleep, outcomes, quality of life

Statement of Significance

Sleep-wake disturbances (SWD) are reported frequently after traumatic brain injury (TBI), but poorly quantified in children with intracranial injuries requiring hospitalization. Our systematic review evaluated this particularly vulnerable subgroup to quantify SWD and risk factors for SWD, showing high rates of fatigue, insomnia, and daytime sleepiness. We secondarily evaluated interventions and the association between SWD and other important posttraumatic morbidities to support SWD as a modifiable target to improve outcomes. While studies support the association between SWD and impairments in cognition, behavior, and quality of life, no studies have compared interventions for SWD. Key limitations of current literature, including the lack of validated and objective measures of sleep, were identified and discussed to guide future work in this important area.

Introduction

Traumatic brain injury (TBI), defined as a disruption of brain function or brain pathology following external force, is a major cause of mortality and morbidity in children and adolescents [1–3]. The severity of TBI is defined by neurologic status at presentation with the Glasgow Coma Scale (GCS; mild 13–15, moderate 9–12, severe 3–8) and imaging results. More than 50,000 children in the United States each year require hospitalization for TBI that results in identifiable pathology on brain imaging, like skull fractures and intracranial bleeding [1]. Survivors of TBI, regardless of severity, report many impairments in physical, cognitive, behavioral, and emotional domains [4, 5]. Some, but not all, impairments are linked to increased severity of the TBI [3, 5–9]. Few modifiable risk factors for impairments have been identified contributing to a lack of effective interventions to improve TBI outcomes [5, 9].

Emerging evidence also suggests a high risk of sleep-wake disturbances (SWD) in children and adolescents after TBI that may persist for years [8, 10]. Three prior systematic reviews [10–12] have assessed SWD after pediatric TBI showing SWD to be a pervasive issue in the months to years after injury. However, this available literature is dominated by concussion patients with the mildest form of brain injury unlikely to require hospitalization, and research shows important differences between concussion and more complicated injuries with respect to demographic, clinical, and treatment characteristics [10, 13–20]. Additionally, children with intracranial pathology on imaging are likely to require intensive care admission, and nearly one-third require a critical care intervention like intubation with mechanical ventilation, sedatives and anesthetics, and antiepileptic medications [3]. Even in pediatric populations without TBI, exposure to critical care admission and interventions increases the risk for long-term morbidity, including SWD [4, 5]. Little data regarding prevalence and risk for SWD exist for children with injuries more severe than a concussion in complicated mild, moderate, and severe TBI requiring hospitalization, who may be at higher risk for SWD.

Healthy sleep is vital for brain maturation, development, and repair of neuronal injury, making children hospitalized with TBI and documented intracranial pathology particularly susceptible to adverse outcomes from SWD [21–23]. Although SWD after TBI are reported, the underlying neurologic mechanism(s) are not clearly established [14]. Potential mechanisms include primary injury to the brain’s structure and connections, and secondary injuries like inflammation, hypoxic or ischemic injury, medication toxicity, and circadian disruption from the hospital environment, all of which are particularly applicable in children with injuries severe enough to require hospitalization [14]. Primary and secondary brain injury also leads to multiple physical, cognitive, and psychosocial sequelae after discharge in these children, and few therapeutic options exist to improve outcomes [5]. There is a strong association between SWD and cognitive, behavioral, and emotional impairments in non-TBI pediatric populations [24–26], and it is essential to investigate SWD as a potentially modifiable target to improve multimodal outcomes after TBI.

We conducted a systematic review to quantify SWD after pediatric TBI among children with complicated mild, moderate, or severe injuries requiring hospitalization. We aimed to delineate the phenotypes of SWD such as insomnia, fatigue, and sleep breathing disorders and to identify risk factors for SWD. We secondarily evaluated interventions for SWD and the association between SWD and other morbidities (cognitive, emotional, physical, and behavioral) and quality of life after TBI.

Methods

Our protocol was created a priori following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidance [27] and registered on with the International Prospective Register of Systematic Reviews (PROSPERO) prior to study commencement (available at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018115619). We performed a systematic search from MEDLINE and PsychINFO to identify studies that included children aged 0–18 years with mild complicated, moderate, or severe TBI requiring hospitalization that reported sleep or fatigue data after hospital discharge. GCS is commonly used to denote the severity of TBI. In this review, we used GCS 13–15 to indicate mild complicated TBI, GCS 9–12 to indicate moderate TBI, and GCS 3–8 to indicate severe TBI. A copy of the MEDLINE search strategy is also published with PROSPERO. Supplementary Table S1 shows the MEDLINE search terms we used. The primary searches were conducted on August 8, 2018 and the MEDLINE search was updated on August 29, 2019. The search strategy was designed to combine key terms in three groups: brain injury, pediatric population, and sleep/fatigue.

Study selection

The following inclusion and exclusion criteria were used for article selection:

1. Participants aged 0–18 years with TBI (mild complicated, moderate, or severe) requiring hospitalization resulting from accidental or intentional injury.

2. Use of self-reported or objective measures for evaluation of sleep or fatigue outcomes after hospital discharge.

3. Published years 1999–present.

4. Included study designs: Randomized controlled trials, nonrandomized trials including time series, prospective and retrospective cohort studies, case–control studies, case series, or reports.

5. Non-English language studies excluded.

6. Nonhuman research or unpublished data excluded.

7. Studies of mixed populations where children with TBI are not reported separately and comprise less than 90% of the studied sample excluded.

8. Concussion only studies or studies of mild TBI without differentiation excluded (concussion defined as head injury without skull fracture or intracranial injury on imaging requiring hospitalization).

From the titles and abstracts identified in the systematic search, two reviewers (ML and CNW) independently performed the initial screening, and discrepancies were resolved with discussion. After the initial screening process was completed and potential titles and abstracts were identified, two reviewers (ML and KMC) screened the full-text articles to identify studies using inclusion and exclusion criteria. Another reviewer (CNW) evaluated discrepancies to determine if the article was eligible for data extraction. After identifying studies for inclusion from the search, a manual review of these articles’ reference lists was performed. Finally, included articles were entered into Scopus to review included articles’ citations. The process was repeated following the updated search. See Figure 1 for the PRISMA diagram detailing the study selection. The majority of studies excluded were due to the wrong population (n = 89 adult, non-TBI, or concussion only studies). The review authors were not blind to the journal titles or to the study authors or institutions.

Figure 1.

PRISMA diagram of study identification for a systematic review.

Data abstraction and synthesis

Two reviewers (ML and CNW) abstracted relevant data from included studies. Data included study author, study year, TBI and control group characteristics, study design, assessments of sleep or fatigue, time to assessment, funding sources, and outcomes related to SWD prevalence and risk factors, associations between SWD and other health outcomes, and SWD interventions. Details of sleep or fatigue measures and study limitations were also extracted. Due to heterogeneity in study design, populations, SWD measures, and outcomes, there was insufficient data to perform meta-analyses. Results of data abstraction were reported qualitatively for each of the study aims.

Risk of bias

The risk of bias was assessed for included observational studies using the Newcastle–Ottowa framework [28]. Potential sources of bias were evaluated by two reviewers (ML and CNW) in the categories of (1) selection, (2) comparability, and (3) outcome or exposure. The overall risk of bias was assigned as low, moderate, or high based on the three categories and the framework’s star ratings. Low risk required more than 6/9 of available stars, at least one star in each of the three categories, and use of sleep- or fatigue-specific measure to assess outcome. Moderate risk of bias required more than 4/9 of available stars and one star in each of the three categories. High-risk studies had 3 or fewer available stars or no stars in at least one category. For the selection category in the framework, representativeness of the population was judged by evaluating the sample size (> or <100 participants), use of consecutive patients, consent or participation rates more than 70%, and limitations of the cohort by TBI severity, language/ethnicity, or age. For the comparability category, the most important factor for control was deemed presence or absence of TBI and secondary factors included age, gender, and socioeconomic status. For the outcome category, a follow-up rate of 75% at least 1 month after injury was deemed adequate. Case series or reports were deemed a high risk of bias and not evaluated by the framework.

Results

Study characteristics

A total of 24 studies were included in the final analysis (Figure 1). Final articles included 20 observational studies (9 cross-sectional [20, 29–36] and 11 prospective [8, 16–19, 37–42]) and 4 case studies or series [43–46]. Studies showed significant heterogeneity with respect to patient age, severity of TBI, length of time from injury to assessment, and measures used to evaluate SWD. Table 1 details included studies and main results. Most studies evaluated older children and adolescents with only eight studies including children under age 4 years [8, 16, 17, 19, 32, 33, 39, 42]. Eight studies included only moderate or severe TBI patients [29, 32, 35, 40, 41, 44–46]. Among prospective studies, time to evaluation ranged from 1 month to 4 years with most providing data on the first year after injury. Cross-sectional studies had variable time to evaluation within and between studies ranging from 1 to 13 years after injury. Eight observational studies evaluated sleep or fatigue primarily [8, 16–18, 29, 30, 35, 37], six included secondary analysis of sleep data as part of a larger study [19, 31, 34, 38–40], and six included sleep data extracted from data reported for other outcomes [20, 32, 33, 36, 41, 42]. Three studies by Crichton et al. [16–18], two studies by Hawley et al. [20, 36], and studies from van Markus-Doornbosch [30] and de Kloet [31] likely have overlapping populations derived from the same larger study population. Two single-patient case studies reported the response of SWD to intervention [44, 46].

Table 1.

Summary of Included Studies

Study first author	TBI group characteristics	Control group	Study design and purpose	Sleep or fatigue assessments	Main results related to SWD or fatigue (prevalence, phenotypes, risk factors, interventions, and impact on other outcomes)	Funding
Prospective studies
Williams et al. [8]	Age 3–18 years N = 78 ABI (TBI, stroke, HIE, infectious, other) n = 40 TBI: 18 mild complicated, 8 moderate, 11 severe	Historical healthy children; nontraumatic brain injury	Prospective cohort study to quantify severity, phenotypes, and risk factors for SWD	SDSC* ,‡; completed at 1–3 months after injury	• Average total SDSC score and the Disorders of Initiation and Maintenance of Sleep subscale score were significantly higher in children with TBI than historical controls • SWD 53% of TBI patients, most severe • Risk of SWD was increased in children with preadmission chronic conditions	Federal
Fischer et al. [37]	Age 8–15 years n = 36 with TBI	Extracranial injury n = 24; and typically developing children n = 27	Prospective cohort evaluating sleep disturbance and behavioral outcomes	SDSC* ,‡; completed at baseline, 6, and 12 months after injury	• Increased total SDSC score after TBI reflecting worse sleep compared to baseline at 6 months • SWD 12 months after TBI were mediated by internalizing problems • SWD were significantly associated with worse externalizing behaviors measured on the CBCL 6 and 12 months after TBI	Federal
Crichton et al. [17]	Age 0–17 years N = 79 TBI: 57 mild, 27 moderate/severe	N/A	Prospective cohort evaluation of risk factors for fatigue after TBI	PedsQL MFS* ,‡ and PIFOS*; completed baseline, 6 and 12 months after injury	• Sleep/rest fatigue was predicted by preinjury fatigue and psychological symptoms preinjury • 6 months after injury, General and sleep/rest fatigue was predicted by physical/motor, sleep, and mood symptoms • Cognitive fatigue was predicted by physical/motor symptoms 6 months after injury • Preinjury fatigue and psychological functioning identified those at greatest risk of fatigue 12 months post-TBI	Private; Federal
Crichton et al. [16]	Age 1–16.9 years N = 109 TBI: 69 mild, 37 moderate/severe	Historical healthy children aged 2–19 years	Prospective longitudinal evaluation of fatigue after TBI	PedsQL MFS* ,‡ and PIFOS*; completed baseline, 6 and 12 months after injury	• Cognitive fatigue worsened steadily over time • Moderate/severe TBI was associated with worse fatigue 12 months after injury compared to mild complicated	Private; Federal
Crichton et al. [18]	Age 8–18 years n = 35 TBI: 27 mild, 5 moderate, 3 severe	Historical healthy children	Prospective observational evaluation of fatigue after TBI	PedsQL MFS* ,‡; completed 6 weeks after injury	• Increased fatigue on PedsQL MFS in TBI patients compared to healthy controls • Fatigue in 62% of TBI patients • Risk factors included depression and sleep disturbance	Private, Federal
Bertisch et al. [38]	Age 8–18 years n = 115 TBI: 86 complicated mild, 29 moderate–severe	N/A	Prospective cohort; evaluation of multiple PROMIS measures’ validity	PROMIS Fatigue* ,‡; completed at 6 months	• Fatigue was common • Convergent validity with the Strength and Difficulties Questionnaire somatic ratings	Federal
Shay et al. [39]	Age 3–6 years old n = 75 TBI: 55 mild– moderate, 20 severe	Orthopedic injury n = 92	Prospective cohort evaluation of sleep disturbances and cognitive and behavioral outcomes after TBI in a secondary analysis of the larger trial	CSHQ* ,‡; completed at 1, 6, 12, and 18 months after injury	• Children with TBI showed more sleep problems than controls • Combined TBI groups showed shorter sleep duration than controls at 6 and 12 months • There is an association between SWD and internalizing and externalizing behaviors, and a significant association between worse SWD and worse executive dysfunction in all TBI severities	Federal
Tham et al. [19]	Age 2–17 years n = 729 TBI: 616 mild, 113 moderate– severe	Orthopedic injury n = 197	Prospective cohort evaluation of sleep problems after TBI as a secondary analysis of the larger trial	Single question extracted from PedsQL General Core*; completed at 3, 12, and 24 months after injury	• All severities of TBI had worsening SWD from baseline after injury • After 2 years, patients with moderate–severe TBI had persistent SWD• Risk factors included increased pain, female gender, psychosocial problems, and non-black race	Federal
Beebe et al. [40]	Age 6–12 years n = 109 TBI: 56 moderate, 53 severe	Orthopedic injury n = 80	Prospective cohort; secondary analysis to evaluate sleep within a larger trial	Sleep questions extracted from CBCL*; completed at baseline, 6, 12, and 48 months	• Increased SWD compared to baseline in severe TBI persisting up to 48 months after injury • 25% of all TBI patients with fatigue at 48 months	Federal
Tilford et al. [41]	Age 5–17 years N = 121 severe TBI	N/A	Prospective cohort evaluation of HRQOL after TBI	The Quality of Well-Being and Child Health Questionnaire*; completed at 3 and 6 months	• Fatigue in 37% • Trouble falling or staying asleep in 25% • No difference when stratifying by GCS cutoff of 5	Federal
Hooper et al. [42]	Age 0–18 years n = 272 hospitalized TBI: 158 mild, 33 moderate, 82 severe	Emergency room treated TBI n = 409	Prospective cohort evaluation of outcomes after TBI	Questions extracted from caregiver interview*; completed at 1, 4, and 10 months	• Increased fatigue and sleep problems in hospitalized TBI at all follow-up points compared to emergency discharged TBI	Federal
Cross-sectional studies
Ekinci et al. [29]	Age 6–18 years n = 20 with moderate–severe TBI and concurrent ADHD	ADHD only controls n = 20	Cross-sectional evaluation of sleep and quality of life in TBI patients with concurrent ADHD	CSHQ* ,‡; completed at 1–4 years after injury	• When compared to children with primary ADHD, the Total Score and Sleep Onset Delay, Daytime Sleepiness, Parasomnias, and Sleep Disordered Breathing subscores of CSHQ were found to be higher in children with TBI and ADHD • SWD risk factors included younger age• There is a significant relationship between worse sleep measured by the CSHQ total score and worse HRQOL in patients with TBI	Unfunded
van Markus-Doornbosch et al. [30]	Age 4–10 years n = 69 TBI	Nontraumatic brain injury n = 19; and historical healthy controls	Cross-sectional evaluation of fatigue after acquired brain injury	PedsQL MFS* ,‡; completed about 2 years after injury	• Increased fatigue in TBI patients compared to healthy controls 2 years after injury • Risk factors included older age and single-parent households	Not reported
de Kloet et al. [31]	Age 5–22 years n = 81 TBI	Nontraumatic brain injury n = 27; and historical healthy controls	Cross-sectional evaluation of family impact after TBI; fatigue secondary analysis	PedsQL MFS* ,‡; completed about 2 years after injury	• Increased fatigue in TBI patients compared to historical controls • There is a significant relationship between worse fatigue and worse scores in the PedsQL FIM total and all subscale scores	Private
Lind et al. [32]	Age 2.5–8.9 months n = 29 severe abusive TBI	N/A	Cross-sectional evaluation of outcomes after abusive TBI	Question extracted from structured interview*; completed at 3.7–12 years after injury	• Sleep problems in 17%	Unfunded
Aaro Jonsson et al. [33]	Age 1–16 years n = 21 TBI: 7 mild, 4 moderate, 10 severe; all neuro- surgically treated	N/A	Cross-sectional evaluation of HRQOL after TBI	Mayo-Portland Adaptability Inventory*; completed 13 years after injury on average	• Fatigue was one of the highest-rated problems among patients with TBI	Private
Osorio et al. [34]	Age 12–18 years N = 102 TBI: 42 complicated mild, 60 moderate–severe	N/A	Cross-sectional evaluation of daytime sleepiness and executive function in a secondary analysis of a larger trial	Parent and child reported Epworth Sleepiness Scale* ,‡; completed at 6 months after injury	• Moderate/severe TBI had increased daytime somnolence compared to those with complicated mild injuries • There is a significant relationship between daytime sleepiness and worse executive dysfunction, both with regard to behavioral regulation and metacognition	Federal
Sumpter et al. [35]	Age 5–16 years n = 15 moderate–severe TBI	Noninjured sibling control n = 15	Cross-sectional evaluation of sleep after TBI	Sleep diary*, family interview*, CSHQ* ,‡, five nights of Actigraphy†; completed at 9–65 months	• Significantly more sleep problems in the TBI group; features consistent with insomnia in the TBI group	Unfunded
Hawley [20]	Age 5–15 years n = 97 TBI: 49 mild, 19 moderate, 29 severe	Participant suggested healthy controls n = 31	Cross-sectional evaluation of symptoms after TBI	Questions extracted from interview*; range 6 months to 5 years after injury	• Increased SWD with moderate-severe TBI versus mild (50% vs 27% within 2 years; 31% vs 12% greater than 2 years after injury)	Federal
Hawley et al. [36]	Age 5–15 years N = 525 TBI: 419 mild, 57 moderate, 49 severe	N/A	Cross-sectional evaluation of outcomes after TBI	Questionnaires*; completed 1–6 years after injury	• Increased SWD with moderate–severe TBI versus mild (20% vs 11%) • Increased fatigue/less active (23% vs 10%)	Federal
Case report or series
Mouthton et al. [43]	Age 4–16 years n = 8 TBI: 5 mild–moderate, 3 severe	N/A	Case series evaluating high-density EEG during sleep after TBI	EEG† completed 1–4.2 months after injury	• Patients with severe TBI had a reduction in sleep slow-wave activity over the midline and an increase over lateral brain areas	Private
Yassin et al. [44]	16-year old with severe TBI	N/A	Case report of narcolepsy without cataplexy after TBI	PSG†, MSLT†, brain MRI†, cerebrospinal fluid orexin level†; completed 18 months after injury	• Sleep onset REM periods were found in three of four onsets of sleep • Sleep latency of 4.5 min • MRI showing reduced hypothalamic and left amygdala volume • Orexin level normal • Intervention: Modafinil daily improved daytime sleepiness	Federal
Busek et al. [45]	n = 3 pediatric patients: 15-, 16-, 18-year olds with TBI	N/A	Case series evaluating sleep architecture after TBI	Daytime EEG† and PSG†; completed at 6–8 months	• All three patients had increased non-REM sleep on PSG • Variability in REM sleep findings based on TBI severity • All patients had areas of focal slowing on daytime EEG	Federal
Andersen et al. [46]	6-year old with severe TBI	N/A	Case report of citalopram use in rehabilitation of TBI	Parent-reported*; completed 3 weeks after injury	• Intervention: Citalopram resulted in a marked improvement in the patient’s sleep	Not reported

ABI, acquired brain injury; ADHD, attention-deficit hyperactivity disorder; CBCL, Child Behavior Checklist; CSHQ, Children’s Sleep Habits Questionnaire; EEG, electroencephalogram; GCS, Glasgow Coma Scale; HIE, hypoxic ischemic encephalopathy; HRQOL, health-related quality of life; MRI, magnetic resonance imaging; MSLT, Multiple Sleep Latency Test; PedsQL FIM, Pediatric Quality of Life Inventory Family Impact Module; PedsQL General Core, Pediatric Quality of Life Inventory General Core Scales; PedsQL MFS, Pediatric Quality of Life Inventory Multidimensional Fatigue Scale; PIFOS, Pediatric Injury Functional Outcome Scale; PROMIS, Patient-Reported Outcome Measurement Information System; PSG, polysomnography; REM, rapid eye movement; SDSC, The Sleep Disturbance Scale for children; SWD, sleep-wake disturbances; TBI, traumatic brain injury.

*Self-reported sleep or fatigue assessment.

^†Objective sleep or fatigue assessment.

^‡Validated sleep or fatigue assessment.

Measures of sleep

Multiple different measures of sleep outcomes after TBI were utilized, including 21 studies with questionnaire or interview, 1 with actigraphy (15 patients) [35], 2 with electroencephalography (EEG; 11 patients) [43, 45], and 2 with polysomnography (PSG; 4 patients) [44, 45]. Among studies using questionnaires, 12 used sleep- or fatigue-specific measure, including the Children’s Sleep Habits Questionnaire (CSHQ; n = 3) [29, 35, 39], Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL MFS; n = 5) [16–18, 30, 31], Sleep Disturbances Scale for Children (SDSC; n = 2) [8, 37], Epworth Sleepiness Scale (ESS; n = 1) [34], and Patient-Reported Outcome Measurement Information System Fatigue Scale (PROMIS Fatigue; n = 1) [38]. Nine studies used subsets of or single questions from nonsleep questionnaires or interview to define sleep and fatigue outcomes [19, 20, 32, 33, 36, 40–42, 46]. Table 2 includes detailed results of observational studies using sleep- or fatigue-specific measures. Supplementary Table S2 contains major topics, number of questions, and scoring of all questionnaires used to evaluate SWD.

Table 2.

Results of Included Studies Detailed by Sleep- or Fatigue-Specific Measures

Measure	Detailed results
Children’s Sleep Habits Questionnaire (CSHQ)		Shay et al. [39]			Ekinci et al. [29]		Sumpter et al. [35]
		Moderate Mean (SD)	Severe Mean (SD)	OI control Mean (SD)	TBI + ADHD Mean (SD)	ADHD control Mean (SD)	TBI Mean (SD)	Control Mean (SD)
	Total score				52.2 (6.5)	44.5 (3.9)	52.1 (6.6)	42.6 (5.4)
	Bedtime resistance				10.0 (2.6)	9.2 (1.3)
	6 months	8.2 (1.8)	9.4 (2.1)	8.1 (1.7)
	12 months	7.6 (1.8)	8.9 (1.9)	8.1 (1.8)
	18 months	7.2 (1.9)	8.6 (1.8)	8.0 (1.8)
	Sleep duration
	6 months	3.9 (1.0)	4.0 (1.2)	3.6 (1.0)
	12 months	3.8 (1.0)	4.4 (1.1)	3.9 (1.1)
	18 months	3.6 (1.0)	4.1 (1.0)	3.6 (1.1)
	Sleep anxiety				5.6 (1.8)	4.8 (0.9)
	6 months	5.7 (1.6)	6.1 (1.7)	5.6 (1.5)
	12 months	5.7 (1.6)	5.6 (1.6)	5.6 (1.6)
	18 months	5.7 (1.6)	5.4 (1.6)	5.5 (1.6)
	Night wakings				4.0 (1.0)	3.5 (0.5)
	6 months	4.3 (1.2)	4.1 (1.3)	4.1 (1.2)
	12 months	3.9 (1.2)	4.1 (1.2)	4.1 (1.2)
	18 months	3.9 (1.2)	3.5 (1.2)	3.9 (1.2)
	Daytime sleepiness				14.3 (3.5)	9.5 (0.9)
	6 months	13.6 (2.7)	12.7 (3.0)	12.9 (2.5)
	12 months	12.8 (2.7)	12.8 (2.7)	13.1 (2.7)
	18 months	12.7 (2.7)	12.6 (2.7)	12.9 (2.7)
	Parasomnias				8.8 (2.0)	6.6 (0.8)
	6 months	9.2 (1.4)	9.2 (1.6)	8.8 (1.3)
	12 months	8.8 (1.4)	9.1 (1.5)	8.8 (1.4)
	18 months	8.8 (1.4)	8.1 (1.4)	8.6 (1.4)
	Breathing disorder				3.6 (1.4)	2.9 (0.3)
	6 months	3.4 (0.7)	3.6 (0.8)	3.4 (0.7)
	12 months	3.4 (0.7)	3.6 (0.8)	3.5 (0.8)
	18 months	3.5 (0.7)	3.5 (0.8)	3.4 (0.8)
	Sleep onset delay				8.1 (1.1)	6.6 (1.2)
Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL MFS)		van Markus-Doornbosch et al. [30]			de Kloet et al. [31]
		TBI Median (IQR)		NTBI Median (IQR)	TBI Mean (SD)	NTBI Mean (SD)
	Total score	79.1 (27.8)		68.1 (31.9)	81.5 (13.7)	73.6 (14.9)
	General fatigue	87.5 (29.2)		75.0 (33.3)
	Sleep/rest fatigue	87.5 (25.0)		79.2 (29.2)
	Cognitive fatigue	79.2 (47.9)		58.3 (29.2)
		Crichton et al. [16]			Crichton et al. [17]		Crichton et al. [18]
		Mild Mean (SD)		Moderate– severe Mean (SD)	TBI Mean (SD)		TBI-Parent Mean (SD)	TBI-Child Mean (SD)
	Total score	79.85 (15.64)		73.73 (22.40)	81.01 (16.91)		69.8 (20.9)	69.3 (19.1)
	General fatigue	81.71 (15.16)		75.35 (24.85)	82.17 (18.05)		68.5 (22.0)	75.1 (17.2)
	Sleep/rest fatigue	81.29 (19.35)		78.59 (2.34)	84.76 (17.30)		68.1 (23.4)	61.9 (21.3)
	Cognitive fatigue	76.55 (22.79)		67.25 (27.70)	76.11 (24.41)		72.7 (22.5)	71.0 (23.2)
Sleep Disturbances Scale for Children (SDSC)				Fischer et al. [37]			Williams et al. [8]
			TBI Mean (SD)	Healthy Mean (SD)	EI Mean (SD)		TBI Mean (SD)	Healthy Mean (SD)
	Total score
	Baseline		41.9 (10.4)	37.7 (6.6)	39.3 (9.3)
	3 or 6 months		43.0 (14.1)	37.7 (8.4)	43.3 (15.8)		38.6 (9.7)	35.1 (7.7)
	12 months		39.7 (10.6)	35.4 (6.3)	41.1 (16.5)
	Initiation and maintenance						12.7 (4.7)	9.9 (3.1)
	Sleep breathing						3.5 (1.0)	3.8 (1.5)
	Arousal						3.3 (1.0)	3.3 (0.8)
	Transition						8.8 (3.7)	8.1 (2.4)
	Hypersomnolence						7.6 (2.8)	7.1 (2.6)
	Hyperhidrosis						2.6 (1.0)	2.9 (1.7)
Epworth Sleepiness Scale (ESS)		Osorio et al. [34]
		Child report Mild Mean (SD)	Child report Moderate–severe Mean (SD)	Parent report Mild Mean (SD)	Parent report Moderate–severe Mean (SD)
	Total score	7.63 (4.21)	6.76 (3.49)	3.67 (1.88)	4.85 (2.29)
PROMIS Fatigue		Bertisch et al. [38]
		TBI-Parent Mean (SD)	TBI-Child Mean (SD)
	Total score	41.3 (11.5)	39.8 (15.0)
Actigraphy		Sumpter et al. [35]
		TBI Mean (SD)	Sibling control Mean (SD)
	Time in bed, h	9:39 (1.07)	9:14 (1.22)
	Total sleep time, h	8:46 (0.54)	8:47 (1.21)
	Wake after sleep onset, h	1:05 (0.15)	0:53 (0.19)
	Sleep efficiency, %	80.02 (3.66)	85.30 (4.82)
	Sleep latency, h	0:50 (0.33)	0:24 (0.21)
	Number wake bouts	30.24 (7.32)	27.88 (6.61)
	Wake-bout duration, min	2.13 (0.23)	1.90 (0.23)
	Fragmentation index	27.66 (6.30)	28.06 (8.34)
	Interdaily stability	0.73 (0.14)	0.70 (0.10)
	Intradaily variability	0.72 (0.21)	0.81 (0.29)
	Relative amplitude	0.95 (0.03)	0.95 (0.02)

ABI, acquired brain injury; ADHD, attention-deficit hyperactivity disorder; DA, disorder of arousal; DIMS, disorders of initiation and maintenance of sleep; EI, extracranial injury; HSom, hypersomnolence; NTBI, nontraumatic brain injury; SBD, sleep breathing disorder; SH, sleep hyperhidrosis; SWTD, sleep-wake transition disorders; TBI, traumatic brain injury.

SWD prevalence

Ten studies reported prevalence of SWD [8, 18, 20, 32, 34, 36, 37, 40–42]. Figure 2 summarizes extracted data on the prevalence of SWD by severity and time since injury. Within 6 months of injury, more than 20% of reported children with TBI had trouble falling or staying asleep, fatigue, daytime sleepiness, and nightmares. Prevalence was similar at all time points for most SWD evaluated. Evaluated studies had significant heterogeneity limiting direct comparisons. Time to evaluation ranged from 1 month to 12 years after injury, and most studies limited evaluation to older children and adolescents with only three studies evaluating prevalence in children under age 5 years [8, 32, 42]. One study included all hospitalized TBI without differentiation of severity [37], three studies included only moderate or severe TBI [32, 40, 41], and six studies included mild complicated, moderate, and severe TBI [8, 18, 20, 34, 36, 42]. All studies measured SWD prevalence with a questionnaire or interview, though none used the same methodology, and only four studies used a questionnaire designed specifically to evaluate SWD or fatigue [8, 18, 34, 37].

Figure 2.

Prevalence estimates for sleep disturbances by injury severity and time since injury among included studies. This figure shows extracted data on the prevalence of SWD by severity and time since injury. Prevalence was similar at all time points for most SWD evaluated.

Baseline (preinjury) SWD

Four studies included a preinjury estimate of baseline SWD by a retrospective questionnaire. All showed increased SWD after injury compared to baseline, but used different measures, patient characteristics, and time to evaluation. Beebe et al. [40] showed increased SWD compared to baseline in severe TBI persisting up to 48 months after injury. Fischer et al. [37] showed an increased total SDSC score after TBI reflecting worse sleep compared to baseline at 6 months, but the difference did not persist at 12 months. Tham et al. [19] showed all severities of TBI had worsening SWD from baseline after injury using a single question regarding trouble sleeping; after adjusting for demographic factors, patients with moderate–severe TBI had persistent SWD 2 years after injury compared to baseline. Crichton et al. [18] found increased fatigue at 6 months compared to baseline in all TBI severities.

Comparison of SWD after TBI to other populations

Thirteen studies evaluated SWD after TBI compared to other pediatric populations, including orthopedic injury [19, 37, 39, 40], other nontraumatic brain injuries [8, 30, 31], or healthy/noninjured children (five using historical controls) [8, 16, 18, 20, 29  –31, 35, 37]. Compared to patients with orthopedic injuries, three studies evaluating children with TBI across the age spectrum found more SWD in both short- and long-term follow-up as measured on the CSHQ [39], as well as nonsleep-specific questionnaires [19, 40]. Fischer et al. [37] found similar scores on the SDSC between TBI and non-TBI injury controls at 6 and 12 months postinjury, but the TBI group did have more SWD than healthy controls. Williams et al. [8] also found significantly higher SDSC scores 3 months postinjury, indicating more SWD in patients with TBI than healthy controls. Sumpter et al. [35] found increased sleep disturbance on the CSHQ and actigraphy when comparing TBI patients to healthy siblings a median of 2 years after injury. Hawley [20] similarly showed higher rates of sleep problems and nightmares in TBI patients versus healthy controls. Four studies showed increased fatigue on the PedsQL MFS in TBI patients compared to historical healthy controls 6 weeks after injury [18], 12 months after injury [16], and 2 years after injury [30, 31]. When comparing TBI to nontraumatic forms of brain injury approximately 2 years postinjury, two studies showed more fatigue in the non-TBI group using the PedsQL MFS [30, 31]. Another study used the CSHQ to show patients with TBI and concurrent attention-deficit hyperactivity disorder (ADHD) had worse SWD across multiple domains compared to children with ADHD alone [29].

TBI severity and SWD

The risk of SWD was evaluated by 15 studies with respect to TBI severity. Results were variable, but all studies used different methodologies, had different patient populations, and variable time since injury. Of the eight studies using a sleep-specific questionnaire, most showed no difference by severity. Using the CSHQ total score, two studies showed no difference between severe TBI and other TBI severities [29, 39]. Similarly, using the SDSC, Fischer et al. and Williams et al. showed no difference by GCS [8, 37]. Using the PedsQL MFS, worse fatigue was observed in moderate–severe TBI compared to mild complicated TBI in one of three studies [16]. Osorio et al. [34] showed increased daytime sleepiness on the ESS in moderate–severe TBI versus mild TBI. Studies using questions extracted from other nonsleep questionnaires most often did show differences by severity. Beebe et al. [40] showed higher overall sleep concerns in severe TBI versus moderate when controlling for baseline SWD. Three studies using single questions showed increased trouble sleeping with moderate–severe TBI versus mild TBI [19, 20, 36], and two studies similarly showed differences in fatigue [20, 36]. Tilford et al. [41] failed to show differences in trouble sleeping or fatigue on single questions in a study on severe TBI when dichotomizing at a GCS of 5.

Risk factors for SWD

Seven studies evaluated other risk factors for SWD after TBI, including age, gender, comorbidities, and race, but there was considerable heterogeneity in these studies with respect to populations, measures of SWD, and risk factors evaluated. Predictors of fatigue were evaluated by four studies ranging from 6 weeks to 2 years after injury using different populations and methodology. These studies that reported risk factors for fatigue included depression [17, 18], sleep disturbance [17, 18, 37], older age [30], preinjury fatigue [17], and single-parent households [30]. Ekinci et al. [29] showed that worse SWD as measured by the total score of the CSHQ were associated with younger age. Tham et al. [19] showed that worse SWD as measured by a single question regarding trouble sleeping were associated with increased pain, female gender, psychosocial problems, and non-black race. Using the SDSC, Fischer et al. [37] showed that SWD 1 year after TBI were mediated by internalizing behaviors. Williams et al. [8] showed an increased risk of SWD in children with preadmission chronic conditions.

Phenotypes of SWD

Thirteen studies reported fatigue after TBI ranging from 6 weeks to 13 years after injury and show fatigue is common morbidity after TBI. Only six studies used a fatigue-specific questionnaire (n = 5 PedsQL MFS; n = 1 PROMIS Fatigue), while others reported results of single questions extracted from other questionnaires. Results of two studies using the PedsQL MFS showed similar average values for total fatigue score and that nontraumatic brain injuries had worse fatigue than TBI patients, though both groups had worse fatigue than healthy children [30, 31]. Three studies by Crichton et al. [16–18] also used the PedsQL MFS 6 weeks, 6 months, and 12 months after TBI and showed significantly worse fatigue than healthy populations for the total and all subscale scores. Nearly 50% of patients had severe fatigue as rated by parents in one of these studies [18]. Beebe et al. [40] showed more than 25% of moderate–severe TBI patients had fatigue up to 4 years after injury.

Six studies reported other SWD phenotypes. Two studies reported phenotypes using the subscales of the CSHQ including sleep duration, bedtime resistance, sleep onset delay, sleep anxiety, night wakings, daytime sleepiness, parasomnias, and sleep breathing disorders [29, 39]. However, these studies evaluated different patient populations at different time points and found different results. Shay et al. [39] found greater bedtime resistance in the severe TBI group at 6 months and shorter sleep duration with any TBI compared to injury controls in young children at 6 and 12 months after injury. Ekinci et al. [29] found worse sleep onset latency, daytime sleepiness, parasomnias, and sleep-disordered breathing after TBI in older children with concurrent ADHD compared to ADHD controls. Sumpter et al. [35] used actigraphy and found features consistent with insomnia (increased sleep onset latency, poorer sleep efficiency) among children with TBI compared to siblings. Williams et al. [8] found worse SDSC scores for disorders of initiation and maintenance of sleep using the SDSC in TBI compared to healthy children. Osorio et al. [34] found increased daytime sleepiness in adolescents with moderate–severe TBI versus mild complicated TBI at 6 months using the ESS. Beebe et al. [40] evaluated individual questions for sleep duration, nightmares, sleep-talking or walking, and bedwetting showing few differences from baseline in these individual phenotypes among moderate and severe TBI groups.

SWD and other outcomes

Five studies evaluated the association between SWD and other posttraumatic morbidities (psychosocial [31, 37, 39] and cognitive [34, 39]) or Health-Related Quality of Life (HRQOL) [29, 31]. De Kloet et al. found a significant relationship between worse fatigue and worse scores on the PedsQL Family Impact Module total score and all subscale scores (worry, communication, family function, and quality of life) approximately 2 years after TBI [31]. Ekinci et al. [29] found a significant relationship between worse sleep measured by the CSHQ and worse HRQOL in patients with TBI and concurrent ADHD. These results were significant for overall HRQOL as well as physical and emotional well-being and family impact subscales. Fischer et al. [37] found SWD were significantly associated with worse externalizing behaviors 6 and 12 months after TBI. Shay et al. [39] similarly found associations between SWD and internalizing and externalizing behaviors in young children with TBI regardless of severity. Shay et al. also found a significant association between worse SWD and worse executive dysfunction in all TBI severities among young children. Osorio et al. [34] similarly found significant relationships between daytime sleepiness and worse executive dysfunction, with regard to behavioral regulation and metacognition, 6 months after TBI in adolescents even when adjusting for TBI severity, medications, and mood problems.

Risk of bias

The potential risk of bias for observational studies is detailed in Table 3 with all having moderate or high risk of bias. Five prospective studies and two cross-sectional studies had a moderate risk of bias. Common sources of bias included small sample sizes, low consent or participation rates, inclusion/exclusion criteria limiting generalizability, lack of control populations without brain injury, high attrition rates, and measurement of sleep outcomes without validated tools or objective measures.

Table 3.

Risk of Bias Assessment for Observational Studies (Newcastle–Ottowa Framework)

	Potential sources of bias
Study first author	Selection	Comparability	Outcome	Overall risk of bias (star rating)
Prospective studies
Tham et al. [19]	• Secondary analysis of larger trial • Consent rate 61%	• Orthopedic controls differed in race, ethnicity, socioeconomic status, mechanism of injury	• Parent-reported outcome • Single question extracted from a nonsleep questionnaire measured outcome	Moderate (7/9)
Beebe et al. [40]	• Secondary analysis of larger trial • English speaking only • Age limited to 6–12 years • No report of consent rate	• Some patients in the TBI group also had an orthopedic injury • Control group of lower socioeconomic status	• Parent-reported questionnaire • Extracted questions on the CBCL • Attrition rate ranged 14%–28% • Variable timeframe to assessment	Moderate (6/9)
Fischer et al. [37]	• Small sample (n = 87) • Age limited to 8–15 years • English speaking only • Limited by geographical residence • No report of consent rate	• Groups differed by gender	• Parent-reported questionnaire • Attrition rate more than 25%	Moderate (5/9)
Shay et al. [39]	• Secondary analysis of larger study • Age limited to 3–6years • English speaking only • Consent rate 41% • Retrospective recall of preinjury sleep	• Some patients in the TBI group also had an orthopedic injury • Groups differed by the mechanism of injury	• Parent-reported questionnaire • Attrition rate more than 25%	Moderate (5/9)
Williams et al. [8]	• Small sample (n = 40) • No baseline measures	• Historical control data • Nontraumatic brain injury group not compared to TBI	• Parent-reported questionnaire	Moderate (5/9)
Bertisch et al. [38]	• Study not designed for sleep outcomes • Age limited to 8–18 years • English speaking only • Consent rate 55% • No baseline measures	• No control group	• Parent-reported questionnaire	High (4/9)
Crichton et al. [16]	• Secondary analysis of larger study • Baseline assessment not the primary outcome measure	• Historical control data only and differed on age, race, gender from TBI sample • TBI severity groups differed by age, mechanism	• Parent-reported questionnaire • Attrition rate more than 40% varying by age, ethnicity, and severity	High (4/9)
Crichton et al. [17]	• Secondary analysis of larger study • Only 50% of the original cohort were included and differed by race from excluded • Baseline assessment not the primary outcome measure	• No non-TBI control group	• Parent-reported questionnaire	High (4/9)
Crichton et al. [18]	• Secondary analysis of larger study • Age limited to 8–18 years • Small sample size (n = 32) • English speaking only • No baseline measures	• Historical control data only	• Parent-reported questionnaire • Attrition rate 26%	High (3/9)
Hooper et al. [42]	• No baseline outcome measures • No consent rate reported • Geographically limited sample	• No non-TBI control • ER versus hospitalized TBI groups differed by preinjury special education needs, mechanism of TBI	• Parent interview for outcome • Attrition rate 1 month 45%; 4 months 64%; 10 months 88%	High (3/9)
Tilford et al. [41]	• Study not designed for sleep outcomes • Age limited to 5–17 years • English speaking only • All patients had mechanical ventilation • No baseline outcome measures • Consent rate not reported	• No control group	• Parent-reported questionnaire • Single questions extracted for sleep outcomes • Attrition rate 41% 3 months; 33% 6 months	High (2/9)
Cross-sectional studies
Sumpter et al. [35]	• Small sample size (n = 15) • Consent rate 32% • Age limit 5–16 years • Limited to moderate or severe TBI • Retrospective interview to assess baseline sleep	• Sibling controls	• Multiple sleep outcome measures, some parent/child report • Variable time to assessment, range 9–65 months	Moderate (6/9)
Hawley [20]	• Study not designed for sleep outcomes • Age limited to 5–15 years • Participation rate 14% • No baseline assessments	• Healthy control group derived from participant suggestion	• Participant interview • Single questions extracted for sleep outcomes • Variable time to assessment, range 1–6 years	Moderate (5/9)
de Kloet et al. [31]	• Secondary analysis from larger study • Not designed for sleep outcomes • Consent rate 60% • No baseline assessment of outcome	• Control group with nontraumatic brain injury • Comparability of brain injury groups not reported	• Parent-reported questionnaire • Fatigue outcome from a secondary questionnaire • Attrition rate 27%	High (4/9)
Ekinci et al. [29]	• Secondary analysis of larger study • Small TBI sample (n = 20) • Age limited to 6–18 years • Limited to moderate–severe TBI with ADHD • No baseline outcome assessments	• Non-TBI ADHD control • Small control sample (n = 20) • Groups differed by gender • No mention of recruitment rates for the control group	• Parent-reported questionnaire • Variable time to assessment	High (4/9)
van Markus-Doornbosch et al. [30]	• Secondary analysis of larger trial • Limited to Dutch speaking • Consent rate 33% • No baseline outcome assessment	• Control group with nontraumatic brain injury • Groups differed by age	• Parent/child reported questionnaires • Attrition rate 38%	High (4/9)
Aaro-Jonsson et al. [33]	• Study not designed for sleep outcomes • Small sample; low participation (n = 21; 46%) • All patients had the neurosurgical intervention • No baseline assessments	• No control group	• Participant interview • Single questions extracted for sleep outcomes • Variable time to assessment, average 13 years	High (2/9)
Hawley et al. [36]	• Study not designed for sleep outcomes • Age limited to 5–15 years • Response rate 56% • No baseline outcome assessments	• No control group	• Parent survey • Single questions extracted for sleep outcomes • Variable time to assessment	High (2/9)
Lind et al. [32]	• Study not designed for sleep outcomes • Small sample size (n = 29); 60% participation • Limited to abusive head trauma • No baseline assessments	• No control group	• Parent interview • Single question extracted for sleep • Variable time to assessment, average 8 years	High (2/9)
Osorio et al. [34]	• Secondary analysis of larger study • Age limited to 12–18 years • Consent rate 63% • No baseline outcome assessment	• No control group, compared by TBI severity	• Parent/child reported questionnaire • Attrition rate 52%	High (2/9)

ADHD, attention-deficit hyperactivity disorder; CBCL, Child Behavior Checklist; SWD, sleep-wake disturbances; TBI, traumatic brain injury.

Discussion

This systematic review demonstrates that SWD are a common and persistent problem for pediatric TBI survivors in the months to years following hospital discharge that place patients at risk for cognitive, behavioral, and HRQOL impairments. Included studies show that one in five patients has some type of SWD after discharge regardless of TBI severity or patient age, though data in young children are very limited. Studies show statistically significant differences in SWD outcomes between TBI and control populations and important increases in SWD from preinjury baseline. No data evaluated the effectiveness of interventions to treat SWD after pediatric TBI outside of two single-patient case reports. Among available studies, there is considerable heterogeneity among measures defining SWD, populations, and time from injury to evaluation. The overall quality of evidence is low, with few studies using sleep-specific questionnaires or objective measures of sleep, and few studies are designed to specifically evaluate SWD after TBI. Due to limited evidence, many important knowledge gaps remain regarding the prevalence of specific SWD phenotypes, risk factors for SWD, interventions to treat SWD, and whether treating SWD can secondarily improve other posttraumatic morbidities.

A key barrier identified in this review to advancing our understanding of SWD after pediatric TBI is variability in measures used to identify and define SWD. A recent review of pediatric sleep measures identified hundreds of published tools, but few measures that had been fully validated [47]. Differences in prevalence of SWD, risk factors for SWD, and phenotypes of SWD were noted between studies that used sleep-specific measures versus other tools to define SWD outcomes. Among this select population of hospitalized pediatric TBI survivors, little data exist on the performance of these tools with respect to reliability and validity. In addition, each sleep questionnaire used different definitions for sleep phenotypes (i.e. insomnia, parasomnias), which can contribute to inconsistency among studies. PSG and EEG are considered the gold standard for evaluation of some SWD phenotypes [48], but only data from small case series were found using these objective tests. Actigraphy has also been recommended by the American Academy of Sleep Medicine for the evaluation of some SWD phenotypes like insomnia and circadian disturbances [49]. However, actigraphy data were provided in only one study of 15 TBI patients. Additionally, for many included studies, the same questionnaires were used to measure for both SWD and the other morbidities we assessed, regardless of the validity of the measure. For most, the same reporter was used when assessing the questionnaires, which can artificially inflate associations due to shared method and shared reporter variance. A lack of objective measurements and the availability of reliable and valid questionnaires in this population introduces bias and limits our understanding of SWD epidemiology after TBI. Future studies should evaluate SWD in pediatric TBI with validated sleep-specific questionnaires and objective measures of sleep, with strict phenotype definitions based on an accepted criterion.

A second key barrier is an unavoidable heterogeneity across the pediatric TBI population. Among TBI patients, considerable differences occur with respect to the location of brain injury, mechanism of brain injury, other concurrent injuries, and presence of secondary brain injury from inflammation, seizures, and ischemia [9, 50]. Additionally, patient age is a significant factor to consider with respect to brain maturity, developmental level, sleep patterns, and differences in measurement techniques. Many of the studies we identified limited evaluation of SWD by TBI severity or age, but few studies evaluated similar populations which limited direct comparison of findings. Data among young children were particularly limited, and this remains an under-evaluated population in sleep research. Additionally, comorbidities are likely an important consideration with respect to SWD after TBI, as disorders like ADHD are known to increase risk, and may be particularly important in regard to the phenotype of SWD. However, several studies did not report details of these key demographic and clinical variables limiting the comparability and generalizability of their findings. Future work should consider this population heterogeneity in all study phases from design through statistical analysis and dissemination to improve our understanding of risk factors for SWD.

A third key barrier is the lack of consistency between studies with regard to timing of evaluation, which is likely to influence the evaluation of prevalence, risk factors, and association with recovery from TBI. Included studies assessed SWD outcomes 1 month to 12 years after injury and only four studies evaluated preinjury estimates of SWD. Repeated measures of SWD were uncommon in included studies, and among studies that did assess outcomes at multiple time points, few evaluated longitudinal trajectory of SWD outcomes. It remains unclear if SWD improve, persist, or worsen after discharge, and future studies should evaluate the trajectory of SWD after TBI.

Given the additional lack of studies on interventions we found, it also remains unclear if therapies can alter the trajectory of SWD in these children or if altering SWD can improve other outcomes. Clinicians currently have no evidence-based therapies to improve SWD after TBI, and guidance on best practices in management is lacking [5]. Future studies need to investigate pharmacological, psychological, and behavioral interventions for SWD in order to determine safe and effective strategies for managing this common morbidity.

We limited our review to a subset of TBI patients aged 0–18 years requiring hospitalization for mild complicated, moderate, or severe injuries. These patients are likely at the highest risk for harm from SWD given the importance of sleep in brain development and neuronal healing [21–23]. Our results were similar to those of adult TBI studies as well as pediatric concussion studies showing pervasive SWD [10, 14]. SWD, including insomnia and daytime fatigue, are some of the most commonly reported symptoms following pediatric concussion and are shown to prolong recovery from concussion, as well as correlate with other post-concussive symptoms including physical, cognitive, and mood outcomes [13]. Among adult TBI populations of all severities, insomnia is reported in 30%–60%, parasomnias in 25%, and excessive daytime sleepiness in more than 50% [14]. Studies similarly show important relationships between sleep and other posttraumatic morbidities after adult TBI [14]. Taken together, our review further highlights the importance of evaluating SWD after hospitalization for TBI in these vulnerable children.

Our review methodology has some limitations to consider. We excluded unpublished literature, such as those from conference presentations or abstracts, and included searches from two databases. We limited our studies to the English language, so a few studies from other countries were excluded, limiting our work’s generalizability to those populations. We also limited our inclusion to recent works published after 1999. It is possible that other articles were not retrieved that were applicable to our goals, but given the limited number of studies we found using our comprehensive search strategies and literature showing an upswing in pediatric sleep research within the last 20 years [51], it is unlikely a significant number of relevant studies were not retrieved or that our results would differ.

Conclusions

SWD are an important morbidity after pediatric TBI with implications for patient recovery in multiple health domains. Current literature is sparse and leaves many gaps in knowledge regarding the prevalence of SWD, including phenotypes and risk factors. Little data exist on how SWD impact important patient outcomes with respect to cognitive, physical, and psychosocial health, but SWD may represent a key modifiable risk factor for poor health and quality of life after TBI. Importantly, we identified no studies comparing interventions to treat SWD after pediatric TBI. Filling gaps in our understanding of the impacts of SWD after pediatric TBI is the first step toward identifying interventions to treat this important morbidity.

Acknowledgments

We acknowledge Ms Jalane Jara for her assistance in compiling full-text articles during the conduct of the review.

Funding

CNW is supported by the Agency for Healthcare Research and Quality (K12HS022981). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.

Conflict of interest statement. None declared.