OBJECTIVE: To assess children and adolescents with severe fatigue who are referred to pediatricians and to examine whether factors can be identified at their first visit that predict worse outcomes at 1 year.
METHODS: Ninety-one patients, aged 8 to 18 years completed questionnaires about sleep, somatic symptoms, physical activity, and fatigue. They were reassessed 12 months later. Measurements at baseline and outcome were analyzed by using univariable logistic regression with persistent, severe fatigue (yes/no) and persistent school absence (yes/no) as dependent variables and baseline scores as independent variables.
RESULTS: After 12 months, 50.6% of the children and adolescents showed improvement; 29.1% had persistent fatigue, and 20.3% had persistent fatigue with significant school absence. Factors associated with the poorest outcome were sleep problems (odds ratio [OR]: 1.4 [95% confidence interval (CI): 1.1–1.8]), initial fatigue score (OR: 1.1 [95% CI: 1.0–1.2]), somatic complaints such as hot and cold spells (OR: 1.9 [95% CI: 1.2–3.0]), blurred vision (OR: 2.1 [95% CI: 1.1–4.0]), pain in arms and legs (OR: 2.0 [95% CI: 1.0–3.2]), back pain (OR: 1.8 [95% CI: 1.0–3.2]), constipation (OR: 1.7 [95% CI: 1.0–2.7]), and memory deficits (OR: 1.8 [95% CI: 1.0–3.2]). Resolved fatigue was associated with male gender (OR: 5.0 [95% CI: 1.6–15.5]) and a physically active lifestyle (OR: 1.3 [95% CI: 1.1–1.5]).
CONCLUSIONS: Assessment of predictive factors at the first visit enables the pediatrician to identify those patients with severe fatigue who are at risk of a poor outcome. Female gender, poor sleep quality, physically inactive lifestyle, and specific somatic complaints were important predictive factors.
- persistent school absence
- persistent fatigue
- somatic symptoms
- physically active lifestyle
Fatigue is a universally experienced but not well understood symptom. In a Dutch survey of an adolescent school-based population, 20.5% of the girls and 6.5% of the boys reported severe fatigue, of whom 80% and 61.5%, respectively, reported fatigue lasting 1 month or more.1 In most cases, the fatigue will disappear spontaneously over time. A small percentage of fatigued adolescents will seek medical advice. For these patients, it is of great importance to know the risk factors for the persistence of fatigue. Persistent fatigue has a negative impact on education and career plans, particularly through failure to attend school.2–4 Most studies on fatigue focus on chronic fatigue syndrome (CFS) as defined by the Chronic Fatigue Syndrome Study Group.5 Little is known about children and adolescents who do not meet CFS criteria but nevertheless have complaints of ongoing debilitating fatigue and are seeking medical help. The purpose of our study was to determine those factors that predict the outcome for children and adolescents who present to the pediatrician with fatigue as their most dominant symptom.
Lack of refreshing sleep is 1 of the key symptoms of CFS.5 Moreover, fatigued adolescents experience a variety of physical complaints such as headaches, muscle and joint pains, and abdominal pain.6–9 Both poor sleep quality and these concomitant somatic symptoms might be associated with poorer outcomes for children and adolescents with fatigue. The level of exercise the patient was engaged in before the onset of fatigue may be another important prognostic factor. Little10 and much11–13 physical activity in sports both are known risk factors for the development of CFS.
We assessed the associations between gender, severity of fatigue, sleep quality, somatic symptoms, and physically active lifestyle at baseline and the persistence of fatigue with or without significant school absence in the subsequent year.
Ninety-one patients aged 8 to 18 referred to 1 of 30 pediatricians from 10 Dutch nonacademic hospitals between 2003 and 2006 with the main symptom of disabling fatigue were included in this study. All patients underwent a thorough clinical evaluation by their pediatrician to identify possible underlying or contributing conditions of somatic or psychiatric morbidity. In the study period (12 months), none of the patients received a final medical explanation for the fatigue complaints. At the first appointment, and after 12 months, the patients filled out questionnaires at home. The general treatment by the pediatrician consisted of reassurance and encouragement to attend school as much as possible. Half of the patients received, as part of a randomized, controlled trial, a video film about chronic fatigue and how to cope with it.
Fatigue was measured at baseline and at 12 months with the subjective fatigue subscale of the validated Dutch version of the self-report questionnaire Checklist Individual Strength (CIS-20), which consists of 8 items about fatigue experienced in the 2 weeks preceding the assessment, using 7-point Likert scales (range: 8–56 points). The questionnaire has good reliability and discriminative validity.14 Persistent fatigue was defined as a subjective fatigue subscale score of ≥40 on the CIS-20 at 12 months, and persistent fatigue with significant school absence was defined as persistent fatigue plus a school absence of >50%. School absence was measured by missed school classes divided by the total number of scheduled classes in the previous 4 school weeks.
Somatic complaints were assessed at baseline with the validated Dutch version of the Children's Somatization Inventory (CSI),15 a self-report questionnaire, rating the presence of 35 somatic symptoms in the 2 weeks preceding the assessment, using 5-point Likert scales. A total score, representing both number and severity of symptoms, was obtained by summing the ratings (range: 0–140).
Sleep problems were measured at baseline and at 12 months by a sleep questionnaire (Appendix). This short questionnaire was developed for this study and offers insight into the quality of sleep as perceived by the children and adolescents themselves. Each item was scored on a 5-point Likert scale.1–5 The total score was obtained by summing the ratings (range: 5–25). The higher the score, the more sleep problems that exist.
Physical activity as part of the lifestyle before onset of the fatigue complaints was measured by a questionnaire, with 6 items asking about regular exercise in the year preceding the fatigue adding up to a total score between 0 and 15 (Appendix). The membership of sports clubs is a separate item because, in the Netherlands, sports clubs are not related to schools and membership points at a more active lifestyle within a social context. Separate validation studies for the sleep quality and physical activity questionnaires were not performed.
The medical ethics committee of the University Medical Centre Utrecht approved the protocol of this study. Assent was obtained from all patients and/or their legal guardians.
For the distribution of baseline patient characteristics and baseline data of fatigue, sleep, and somatic symptoms, descriptive statistics were used (means and SDs).
To identify predictive factors at baseline for the persistence of fatigue with or without school absence 12 months later, the data were analyzed with univariable logistic regression by using the CIS-20 subjective fatigue subscale ≥40 (yes/no), CIS-20 subjective fatigue subscale ≥40 plus significant school absence (>50%) (yes/no), and resolved fatigue (yes/no) at the 12-month follow-up as dependent variables. Regular exercise, sleep quality score, CSI score, and specific somatic symptoms were analyzed as independent variables. Multivariable logistic regression with the same outcome variables was used to examine the independence of factors that were univariably associated with outcome measures. Results are expressed as odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and gender, indicating the odds of having the dependent variables after 12 months, in the presence of the factor or symptom compared with the absence of that factor or symptom at the first visit, irrespective of age and gender. Statistical significance was considered to be reached when the 95% CIs did not include 1, corresponding to a P value of <.05.
All analyses were performed by using SPSS 14.0 (SPSS Inc, Chicago, IL).
Ninety-one patients (72.5% girls) were included with a mean age of 14.0 (SD: 2.1) years. All patients were white. Fatigue complaints started 6.7 months (SD: 4.8) before the first visit to the pediatrician (median: 5.0 months). At follow-up 12 months later, 79 patients (72.1% girls, aged 15.0 (SD: 2.0) years) participated in the study (86.8%). Table 1 shows the baseline characteristics of the total group of patients and of the 3 different outcome subgroups. After 12 months, perceived severity of fatigue of the total group was decreased from a score of 46.7 (SD: 8.8) to 36.1 (SD: 14.1), school absence from 50.1% to 19.4% (SD: 30.4), and sleep quality from a score of 13.8 (SD: 3.4) to 13.1 (SD: 3.5).
Table 2 shows predictors for the outcome at 12 months expressed as ORs. At the 12-month follow-up, 23 patients (29.1%) had a fatigue severity score of ≥40 Likert points, without significant school absence. They were classified as having persistent fatigue. Sixteen patients (20.3%) were classified as having persistent fatigue (≥40 Likert points) with significant school absence. In 40 patients (50.6%) the fatigue was resolved.
The odds of developing persistent fatigue with significant school absence were 40% (OR: 1.4 [95% CI: 1.1–1.8]) higher for 1 Likert point increase on the sleep quality questionnaire and 10% (OR: 1.1 [95% CI: 1.0–1.2]) higher for 1 Likert point on the subjective fatigue subscale. A physically active lifestyle before the onset of fatigue reduced the odds of persistent fatigue with significant school absence by 30% (OR: 0.7 [95% CI: 0.5–0.9]), being a member of a sports club reduced the odds by 90% (OR: 0.1 [95% CI: 0.0–0.5]), and regular cycling from home to school (mean: 36.6 minutes per day [SD: 38.0]) reduced the odds by 60% (OR: 0.4 [95% CI: 0.2–0.8]). The CIS-20 and the total score of the CSI did not predict persistent fatigue with significant school absence. Nevertheless, some somatic symptoms such as blurred vision (OR: 2.1 [95% CI: 1.1–4.0]), hot and cold spells (OR: 1.9 [95% CI: 1.2–3.0]), memory deficits (OR: 1.8 [95% CI: 1.0–3.2]), constipation (OR: 1.7 [95% CI: 1.0–2.7]), pain in the arms and legs (OR: 2.0 [95% CI: 1.0–3.2]), and back pain (OR: 1.8 [95% CI: 1.0–3.2]) were significantly associated with persistent fatigue with significant school absence.
The odds of developing persistent fatigue without school absence were also 10% (OR: 1.1 [95% CI: 1.0–1.2]) higher for 1 Likert point on the subjective fatigue subscale. Despite being a predictor for persistent fatigue with significant school absence, sleep problems and previous physically active lifestyle did not predict persistent fatigue without significant school absence. Neither was the CSI total score predictive, but some somatic symptoms from the CSI, low energy (OR: 2.6 [95% CI: 1.2–5.4]), walking difficulties (OR: 2.1 [95% CI: 1.1–3.7]), knee/elbow pain (OR: 1.8 [95% CI: 1.1–2.8]), and fainting (OR: 4.2 [95% CI: 1.0–7.1]), were significantly predictive for persistent fatigue without significant school absence.
Recuperation was significantly associated with being male (OR: 5.0 [95% CI: 1.6–15.5]), having a previous physically active lifestyle (OR: 1.3 [95% CI: 1.1–1.5]), having a membership in sports clubs (OR: 2.1 [95% CI: 1.0–4.3]), and cycling from home to school (OR: 1.8 [95% CI: 1.0–3.3]). Recuperation was adversely associated with severity of fatigue at baseline (OR: 0.9 [95% CI: 0.8–1.0]) and initial presence of sleep problems (OR: 0.8 [95% CI: 0.7–1.0]).
Fatigue in adolescents is quite common and in most cases the fatigue will disappear spontaneously over time.1 Only a small percentage of fatigued adolescents will seek medical advice.16 In the Netherlands, the fatigued adolescents will first consult their general practitioner for advice and examination. In case of ongoing fatigue, the general practitioner will then refer the patient to a general pediatrician, who will investigate further, excluding underlying somatic illnesses and psychological problems, and reassure the patient and parents. In most cases the general pediatrician will advise the patient to avoid complete inactivity, engage in a moderate level of exercise, and attend school as much as possible. However, the prognosis is not always good. If the predictive factors for a poor prognosis were known at the first visit, patients with increased risk of poorer outcome could be referred at an early stage for evaluation and management.
In this group of children and adolescents referred to general pediatricians for fatigue, we found that 49.4% (60% included female patients) had ongoing serious fatigue after 12 months. Female gender was a very strong predictor of a more severe outcome. The percentage of persistent fatigue patients was much higher than in a school-based group of fatigued children,13 where 25.7% of the children were persistently fatigued after 1 year. Not all of the persistently fatigued patients in our study developed significant school absence, with only 16 patients (20.3%) missing >50% of their classes.
The patients in our population scored high on the CSI. This finding corresponds with the substantial overlap of chronic fatigue and somatization syndrome in a general population survey.17 However, the total score on the CSI did not represent a risk factor for poor outcome after 12 months, unlike some particular symptoms. Hot and cold spells, blurred vision, and memory deficits were strong predictive factors for a more negative outcome. These features are part of a complex of symptoms connected to autonomic defects, such as orthostatic intolerance and thermoregulatory dysfunction. Orthostatic intolerance has been described in subgroups of adolescents with CFS.18–21 The patients in our study were not examined by skin cooling tests and head-up tilt tests. The aim of the study was to find symptoms in the history of the patient that could be assessed at the first pediatric visit, instead of performing extensive testing for possible symptoms of autonomic dysfunction.
As known from the literature, sleep problems are associated with CFS,22,23 and lack of refreshing sleep is one of the defining features of the illness.6 The patients in our study were characterized by more sleep problems at the initial evaluation. The more sleep problems at baseline, the higher the probability of developing unfavorable outcomes.
The patients in our population reported little physical activity on a regular basis before their illness. In the Netherlands, 71% of adolescents are members of 1 or more sports clubs.24 Thirty-two percent of the patients who developed persistent fatigue with school absence were members of a sports club before their illness, compared with 75% of the patients who had a more favorable outcome. These findings have striking similarities with the recently published article of Viner et al,25 in which they describe both being highly sedentary or highly active as risk factors for persistent fatigue in adolescents. In our population, only 2 patients were highly active in the period preceding the fatigue. The finding that severely fatigued children with a moderately active lifestyle, especially in sports clubs, have a higher probability of a relatively good outcome corresponds also with a cohort study that showed a strong negative association between playing sports on a regular basis in youth and CFS later in adult life.11
Our findings show that previous physically inactive lifestyle, sleep problems at baseline, and some specific somatic symptoms predict the development of persistent fatigue with significant school absence after 12 months. These factors could easily be recognized at the first doctor's visit and enable earlier evaluation and management. However, intervention studies aimed at preventing persistent fatigue with considerable school absence have not been performed yet. Cognitive behavior therapy might be effective, because it has been shown to be effective for adolescents with CFS.26
Our study shows that fatigued children and adolescents seeking medical care from a general pediatrician are at risk of developing persistent fatigue with significant school absence 1 year later. This has serious implications for education, career, and psychosocial skills. We identified specific factors that predict this serious outcome. The group of fatigued children and adolescents with these factors will need interventions to prevent this outcome.
APPENDIX: QUESTIONNAIRES (INTERPRETED AND COMPLETED BY PATIENTS THEMSELVES)
How often? (never, seldom, sometimes, often, always) (1–5)
Do you wake up unrefreshed?
Do you have a restless sleep?
Do you wake during the night?
Do you have a light sleep?
Do you take daytime naps?
Total sleep problems score (5–25)
Sports club membership (0–2): none, 1, more than 1
Frequency of training (0–2): never, 1 time, more than 1 time per week
Participation in contests (0–2): never, 1 time, more than 1 time per month
Level of sport practice (0–2): not applicable, recreational, (sub)top
Daily cycling (season) (0–2): never, only in summer, always
Daily cycling time (0–3): none, <15 minutes, 15 to 30 minutes, >30 minutes
Daily exercise besides sports club (0–2): never, 1 time, more than 1 time per week
Total regular exercise score (0–15)
We thank the patients and their respective parents and pediatricians for their willingness to participate in this study and Liz and Linda Walker for reviewing the English manuscript.
- Accepted February 26, 2009.
- Address correspondence to Robert J. Bakker, MD, Antonius Ziekenhuis, Department of Pediatrics, Bolswarderbaan 1, 8601 Zk, Sneek, Netherlands. E-mail:
Financial Disclosure: The authors have indicated they have no financial relationships relevant to this article to disclose.
What's Known on This Subject:
Patients with disabling fatigue are not rare in pediatrics, and persistent fatigue has a negative impact on children's education.
What This Study Adds:
Assessment of specific factors in the patient's history that predict a poor outcome can be identified at the first pediatric visit.
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- ↵ter Wolbeek M, van Doornen LJ, Kavelaars A, Heijnen CJ. Predictors of persistent and new-onset fatigue in adolescent girls. Pediatrics.2008;121 (3). Available at: www.pediatrics.org/cgi/content/full/121/3/e449
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