A Scoping Review of Sleep Disturbances in Children and Adolescents with Abdominal Pain Disorders

Introduction

Chronic abdominal pain is very common in youth, particularly adolescents.¹ While identifiable disease is present in some of these children and adolescents, the strong majority will not have a well-defined disease accounting for symptoms. Most will meet criteria for an abdominal pain-associated disorder of gut-brain interaction (AP-DGBI).^2–4 As the name implies, these conditions are believed to arise from an interaction between the gastrointestinal tract and the central and peripheral nervous systems. They are best conceptualized through a biopsychosocial model which recognizes biologic (eg, dysmotility, inflammation, visceral hypersensitivity), psychological (eg, anxiety, depression, coping), and social factors (eg, interactions with family, peers, teachers).⁵ These factors interact with each other, and all can contribute to symptom generation. Sleep is a physiologic function shown to interact with all three of these factors and, as such, may be of importance as a therapeutic target.⁶

There are multiple theoretical factors which provide plausibility for a role for sleep dysfunction to be important in pediatric AP-DBGI: 1. Sleep dysfunction is common in youth, particularly in adolescents, the group with the highest prevalence of AP-DGBIs; 2. Sleep deprivation is associated with a variety of physiologic disturbances across multiple systems relevant to abdominal pain (eg neurologic, inflammatory, cardiac); 3. A bidirectional relationship between sleep and a number of receptors relevant to gastrointestinal functioning (eg, immunologic, endocannabinoid, nitrous oxide signaling, and the stress hormone axis) has been demonstrated in chronic pain patients; 4. Sleep deprivation has strong associations with negative mood, a well-established factor in AP-DGBIs.^7–10 A previous systematic review of sleep problems in pediatric DGBI in general (not specifically abdominal pain-related) demonstrated increased sleep disturbances in association with DGBIs.⁶

Despite the existing theoretical basis implicating sleep disturbances as critical in the conceptualization of pediatric AP-DGBI, empirical evidence appears to be lacking. We undertook this review to assess the current literature for sleep disturbances in youth with chronic abdominal pain regarding their prevalence and pathophysiology, as well as their potential role in outcome in order to identify gaps in knowledge and to determine whether there is an evidential basis for sleep intervention in youth with AP-DGBIs.

Methods

Using the search terms: “sleep disturbances” AND (“abdominal pain”/exp OR “abdominal pain”) AND ([adolescent]/lim OR [school]/lim), we queried PubMed, Embase, Scopus, and Google Scholar yielding an initial 138 articles in children and adolescents (ages 6–18 years. All identified studies were included regardless of cohort size. The articles included in this review were published in English between January 2000 through December 2023. After removing duplicates and reviewing abstracts, we identified 52 articles for full review. After reviewing bibliographies from these articles, another 16 articles were added for full review. Articles were included if they contained data regarding sleep disturbance prevalence, pathophysiology, or relationships to outcome. Two authors independently retrieved relevant data from the articles and any discrepancies in retrieved data were resolved. The final number of articles totaled 32. Of these 32 articles, 24 articles reported prevalence, 18 described associations related to pathophysiology, and 3 had outcome data. These articles form the basis for the current review.

Results

Prevalence

A total of 24 articles reported prevalence rates, including 13 studies assessing abdominal pain patients within a specialty clinic setting and 11 studies assessing patients within a general medical clinic or subjects from a community sample. These studies are summarized in Table 1.^11–34 Prevalence rates varied from 19 to 75% (all but one ≥ 40%) om abdominal pain-specific study groups and from 13 to 53% for subjects reporting abdominal pain in community samples. In the largest abdominal pain cohorts (>200 subjects), prevalence rates for sleep disturbances were 40–45%.

Table 1 Summary of Studies Reporting Prevalence Rates for Youth with Abdominal Pain- Associated Disorders of Gut-Brain Interaction

Sleep disturbances are common in youth with AP-DGBI, with the most common disorders being related to initiation and maintenance of sleep. Sleep disturbances are increased in AP-DGBI over the general population or controls in most but not all studies. When assessing prevalence, there is significant variability in defining sleep disturbances with a general lack of objective measures. The only study that included an objective measure (actigraphy) did not find a difference between abdominal pain patients and controls.¹²

Nine studies compared sleep disturbance prevalence between females and males.^{11,17,18,20,23,24,27,29,30} Three studies demonstrated increased prevalence in females (one of which employed a validated sleep-specific measure), one demonstrated increased prevalence in males, and six demonstrated no difference between sexes (4 of which employed a validated sleep-specific measure.

Pathophysiology

A total of 8 studies assessed associations between sleep disturbances and pain prevalence, pain frequency, and/or intensity with all demonstrating positive relationships.^{15,17,18,20,28,33–35} One of these demonstrated a temporal relationship between sleep disturbances and pain with increased sleep being protective and decreased sleep having a triggering effect on pain.³⁵ Four studies evaluated relationships between sleep disturbances and other gastrointestinal symptoms with associations being demonstrated for nausea (2 studies), heartburn, and diarrhea.^15,26,28,36

The most common associations evaluated were for psychologic disturbances, quality-of-life, and functional disability. Eight studies assessed psychologic disturbances, primarily anxiety and depression, and positive associations were demonstrated in each study.^{11,13,18,28,29,32,36,37} One study reported decreased quality-of life in subjects with sleep disturbances and two reported increased functional disability.^20,23,24

Two studies demonstrated possible mechanisms for sleep disturbances.^21,38 One study found an association between sleep disturbances and screen time and lack of extra-curricular activities.²¹ The other found improvement in sleep disturbances with percutaneous electrical nerve field stimulation (PENFS), though it is not clear whether sleep improved due to improved pain or a more direct effect of PENFS on the brain.³⁸

Outcomes

There has been a paucity of studies assessing the effect of sleep disturbances on outcomes or the effect of interventions on sleep in this patient population with only three such studies identified. In one retrospective study, poor sleep predicted worse outcome in a multi-disciplinary abdominal pain clinic.³⁹ In another study assessing buspirone for patients with abdominal pain, buspirone improved sleep but was not superior to placebo in relief of pain.⁴⁰ In the third study, PENFS resulted in improved sleep, anxiety, pain, mechanical sensitivity, and functional disability.³⁸

Discussion

Sleep disturbances are common in youth with AP-DGBIs and appear to be more common than in the general pediatric population. These findings are consistent with, and build upon, a previous systematic review of sleep problems in pediatric DGBIs in general.⁶ The current review includes 15 manuscripts not included in the previous review. Sleep disturbances appear to be even more frequent in patients with chronic abdominal pain in association with other gastrointestinal symptoms including nausea, heartburn, and diarrhea.^15,26,28,36 Importantly, sleep disturbance is associated with increased pain severity, pain interference, and functional disability as well as lower quality-of-life.^{15,20,23,24,28,33} Sleep disturbance is linked to functional disability through physical symptoms.²⁴ While associations do not assign cause-and-effect, it is likely that pain interferes with sleep and there is empiric evidence for poor sleep enhancing pain.⁴¹ In a momentary assessment study, increased sleep was shown to be protective and decreased sleep to have a triggering effect on pain.³⁵ This finding is similar to what has been reported in adults with IBS where poor sleep predicts higher next day pain.⁴¹ These studies provide evidence for screening youth with chronic abdominal pain for sleep disturbances and intervening when sleep problems are identified.

While subjective sleep measures (ie, survey data) demonstrate increased prevalence of sleep disturbances in youth with AP-DGBI, there is a need for more studies utilizing objective sleep measures. The gold standard for objective sleep measurement is polysomnography, however, this is generally performed in a sleep lab with assessment generally over one night. Actigraphy represents the “gold standard” for naturalistic and longitudinal studies as it is performed in the patient’s usual sleep environment and can be repeated daily if needed. Actigraphy has been validated against polysomnography.⁴² We only identified one study utilizing actigraphy and within this study, increased sleep disturbance was subjectively reported by abdominal pain patients while there were no actigraphic differences in comparison to controls.¹² Mixed findings have also been reported in the broader pediatric pain literature when assessing subjective and objective sleep measures.⁴³

In general, inadequate sleep duration is common in common in children and particularly in adolescents where reported prevalence rates vary from 62 to 75%.⁴⁴ Particularly in adolescents, sleep deprivation is associated with decreased cognitive function and mood disorders.^45,46 Likewise, sleep disturbances appear to be associated with psychological dysfunction, particularly anxiety and depression, in youth with AP-DGBI. Again, these associations are likely bidirectional with anxiety or depression resulting in sleep disturbances and sleep loss, in turn, worsening anxiety and depression. These interactions are likely to have clinical importance as psychological dysfunction has been highly implicated in AP-DGBIs and psychological function has been shown to mediate the relationship between pain and sleep.^38,47,48 In a retrospective study, sleep dysfunction, difficulty relaxing, depression, and older age (ie, teens vs children) were the best predictors of a poorer clinical response in an AP-DGBI population.³⁹ While the interaction between sleep and psychosocial factors have been well studied in general and are among the most studied in patients with chronic abdominal pain, there is a paucity of studies regarding biologic pathways in patients with AP-DGBIs. This is an important area of inquiry as identification of specific pathways may expand our possible points of intervention or provide biomarkers to indicate when sleep deprivation is causing direct biologic dysfunction. A single study of PENFS may provide some insight.³⁸ PENFS has been shown to modulate amygdala function and vagal function, and likely affects numerous other pathways. PENFS resulted in decreased pain, decreased gastrointestinal mechanical sensitivity, and improved sleep.³⁸ It is unclear whether improved sleep was due to decreased pain or a more direct effect, but both began to improve early in the treatment course.

There is a paucity of outcome studies. A single retrospective study demonstrated the ability of poor sleep to predict poorer outcomes, and, among those who did achieve clinical resolution, slower improvement.³⁹ We were not able to identify any studies assessing specific sleep interventions in patients with AP-DGBIs. There is a need for assessing the effects of sleep interventions, alone or in combination with other treatments, on pain frequency and severity, quality-of-life, and functional disability. In addition, given the association between sleep disturbances and mood, there is a need to assess the effect of psychological interventions on sleep and the subsequent impact on pain.

In conclusion, based on high prevalence, there is sufficient evidence to recommend routine screening for sleep disturbance in adolescents with AP-DGBI. There remains a need for more studies utilizing objective sleep measures. Given the broad range of negative physiologic and emotional effects of sleep deprivation, sleep interventions are appropriate when disturbances are identified though it is not yet known the degree to which these interventions will affect the pain experience and resultant disability. Future studies should focus on evaluation of specific sleep interventions on patient outcomes, either alone or as one of multiple interventions, targeting the various relevant components of the biopsychosocial model.