Anxiety, depression, and fatigue in middle-aged and older persons with spina bifida: a cross-sectional study

Abstract

Purpose

To study psychological distress and fatigue among persons with spina bifida (SB) 50 years or older and living in Norway.

Methods

In 2017, cross-sectional data were collected (n = 30). The Hospital Anxiety and Depression Scale (HADS) and the Fatigue Severity Scale (FSS) were used. Descriptive statistics, non-parametric tests, and Spearman correlations were performed. Relevant information from previous studies on adults with chronic spinal cord injury (SCI) and the general population, were collected for comparison.

Results

Participants were 18 women and 12 men, mean age 57.5 (SD 5.6), 26 with myelomeningocele, and six with hydrocephalus. Thirty percent scored above the HADS-A- and 20% above the HADS-D thresholds, thus in the same range as previous studies of SB, but higher compared to persons with SCI and norms. HADS-D correlated with pain and FSS scores. Forty percent reported fatigue symptoms (9/15 without hydrocephalus, 3/6 with hydrocephalus).

Conclusions

The study revealed a high prevalence of fatigue symptomatology among middle-aged and older adults with SB. Symptoms of anxiety and depression were more common than among persons with chronic SCI and norms. SB follow-ups should include awareness of psychological distress and fatigue, and investigate pain and medication side effects among possible influencing factors.

IMPLICATIONS FOR REHABILITATION

• Clinicians treating adult persons with SB should be aware of possible psychological distress and fatigue symptomatology among these patients.

• We suggest an initial screening for psychological distress and fatigue in persons with SB during follow-up visits and rehabilitation.

• Interventions to reduce pain may influence levels of psychological distress and/or fatigue in patients with SB.

• Clinicians should enquire about the effects of medication on fatigue when assessing and prescribing new medications; a thorough medication review helps to assess the benefits and risks.

Keywords:

• Spina bifida
• ageing
• anxiety
• depression
• fatigue
• health care services

Introduction

Spina bifida (SB), specifically myelomeningocele, occurs when the spinal column does not successfully fuse in utero, causing defects in the brain, spinal cord, and bony spinal column [1–3] and a variety of disturbances in cognitive, motor, and sensory function, including bowel, bladder and sexual functions [4]. Less severe types of SB include meningocele and closed spinal dysraphism with skin covering for example a lipomyelomeningocele [1]. SB occulta is a gap in the spine, usually without associated neurologic consequences [1]. This article focuses on SB myelomeningocele and other forms of SB causing neurological deficits.

People with myelomeningocele and other forms of SB causing neurologic deficits often face severe life-long disability and morbidity [5]. SB complexity is related to its level and extent and the presence or absence of hydrocephalus and Chiari II-malformation, and SB can cause extensive health problems, including neuropsychological difficulties that limit self-management [3,6]. The ongoing and complex health- and rehabilitative needs associated with SB have been elucidated, especially the needs for more systematic and coordinated care and follow-up of adults with SB [5,7]. Given the increasing numbers of persons with SB surviving into middle age (50+) and old age (65+) [8], it is essential to address their physical and psychological care needs, as well as to gain a better understanding of facilitators and barriers for participation and quality of life [9–11]. Persons with SB may have a tough process of psychological adjustment or adaptation to additional physical difficulties encountered with advanced age. As physical functioning seem to decrease already at a mean age of 40 years in persons with SB [9], it is particularly important to also examine psychological health aspects.

The 45+ subgroup of the Norwegian Association for Spina Bifida and Hydrocephalus promotes the interests of middle-aged and older adults with SB. They have designated symptomatology indicating psychological distress (i.e. symptoms of depression and/or anxiety) and fatigue as priority areas and suggested more attention to detecting such symptomatology during follow-up health services. An elevated risk for depressive symptoms has been indicated for adolescents with SB, which may be associated with problems with community integration, independence, and social isolation [12]. However, the prevalence of symptoms of psychological distress among adults, including middle-aged and older adults with SB, is less studied. Furthermore, a systematic search in medical databases for studies about fatigue in adults with SB revealed no studies. Fatigue is distinguishable from related symptoms, such as sleepiness, depression, and apathy, and is largely a primary symptom of neurological conditions, such as Multiple sclerosis, Parkinson's disease, myasthenia gravis, traumatic brain injury, cerebral palsy (CP), and stroke [13]. Meanwhile, it may be difficult to differentiate fatigue from depression in a clinical setting, especially in people with SB with cognitive challenges and multiple physical issues. Fatigue is usually understood as a feeling of tiredness, a sensation of exhaustion during or after usual activities, or a feeling of an inadequate energy level to begin these activities. Fatigue is a symptom of a range of conditions and is more frequent in neurological and congenital disabilities than in general populations (GPs) [14]. Although fatigue is one of the most common symptoms in neurology, understanding its pathophysiology is limited [13].

It is particularly important to better understand psychological distress and fatigue symptomatology in persons with SB in their middle age and older adulthood. Therefore, the present study had the following main aims:

1. To determine the prevalence of anxiety, depression, and fatigue symptomatology among persons with SB (any type of SB with neurological deficits) aged 50 years and older and living in Norway.

2. To describe the characteristics of those persons assessed with high scores indicating clinically relevant anxiety, depression, or fatigue symptoms, and study correlations with demographic and clinical factors.

A secondary aim was to compare the proportions of persons with SB indicating clinically relevant anxiety, depression, or fatigue to those of persons with chronic spinal cord injury (SCI) and the GP.

Methods

In 2017, a cross-sectional study of middle-aged (50–65 years) and older adults (>65 years) with SB was conducted [9]. Recruitment for the study was done as follows: (i) All persons with SB born before 1967 identified through the information system at a National Resource Centre for Rare Disorders at Sunnaas Rehabilitation Hospital, Norway, were invited by postal invitations. This information system includes persons diagnosed with specific congenital rare disorders from all over Norway who volunteer to register at the resource centre. By 2016, the number of persons with SB aged ≥50 years was n = 60; and (ii) through advertisements on webpages and at conferences organised by the Norwegian Association for Spina Bifida and Hydrocephalus. The eligibility criteria were as follows: (i) Primary diagnosis of any type of SB with neurological deficits, (ii) ≥50 years of age in 2016, and (iii) Residence in Norway and speaking and understanding the Norwegian language. The exclusion criteria were non-capacity to provide informed consent or to understand the questionnaires, for example, due to serious mental illness (i.e. disorder resulting in serious functional impairment limiting major life activities) or serious substance abuse (alcohol, narcotic drugs). All respondents were contacted on the telephone by one of the researchers for a short interview to ensure that they had understood the study information, fulfilled the inclusion criteria, and schedule an appointment for the data collection. Each person included was then interviewed face-to-face by two researchers (one physiotherapist and one physician) between December 2016 and November 2017. Details on the study design, recruitment process, procedures, and questionnaires are also available in two previous papers [9,15]. Estimations with respect to the representativeness of the study population have been presented in statistical analyses below. The Norwegian Association for Spina Bifida and Hydrocephalus was involved in planning the study. The study was approved by the Regional Committee for Medical and Health Research Ethics in south-eastern Norway and completed in accordance with the Helsinki Declaration.

Measures

From the questionnaire, available as supplemental material in Lidal et al. [9], the following variables were selected:

1. Demographic characteristics; years of education; employment status (employed/not employed);

2. SB severity composite scores, which were estimated based on: (a) shunt status (1 = no, 2 = yes), (b) myelomeningocele (1 = no, 2 = yes), (c) lesion level (1 = sacral, 2 = lumbar, 3 = thoracic), and (d) ambulation status (1 = independent walking, 2 = walkers with aids, 3 = non-walkers) [3]. The total scores ranged from 4 to 10 with higher scores reflecting more severe SB [3]. The internal consistency of the composite in this study population was α = 0.63, while Hommeyer et al. [3] reported a Cronbach’s alpha of α = 0.70;

3. Age at experienced onset of deterioration in gait function; the perceived impact of (a) urinary and/or (b) bowel incontinence on daily life, assessed on a numeric rating scale (NRS) (i.e. from 0 (“no problem”) to 10 (“worst possible problem”); the usage of mental health care services (psychiatrist, psychologist or specialist nurse); daily usage of medications for psychological distress; daily usage of medications that might cause a fatigue side effect. We established the following categories: (1) no usage, (2) one daily medication that might cause fatigue, (3) two medications that might cause fatigue, and (4) more than two medications that might cause fatigue. Medications with a possible fatigue side effect were identified by referencing the Norwegian formulary on pharmaceuticals (“https://www.felleskatalogen.no/medisin/”). We sorted the medications into those (a) never or seldom causing fatigue or “similar” side effects, or (b) often or always causing fatigue or “similar” side effects. “Similar” side effects according to the formulary included somnolence, drowsiness, weakness, sedation, or asthenia.

4. Weight to the nearest kilo (kg), height (cm) and body mass index (BMI) (kg/m²). BMI results were dichotomised into non-obese (BMI up to 29.9) and obese (BMI 30 or above);

5. Subjective health status, which was measured with items 1 and 2 from the RAND 36-Item Health Survey 1.0 Questionnaire (chronic version) [16].

All persons included were assessed with the Hospital Anxiety and Depression Scale (HADS) to measure symptoms of psychological distress [17,18]. HADS includes seven items (each with four response categories: 0, 1, 2, 3) to capture symptoms of anxiety (HADS-A) and seven items to capture symptoms of depression (HADS-D). Scores above eight in HADS-A and HADS-D indicate clinically relevant anxiety or depression symptomatology, respectively [19]. The scores were also summed to a total score (HADS-T).

We applied the Fatigue Severity Scale (FSS) to measure fatigue symptomatology [20,21]. The FSS contains nine items, which are scored on a seven-point Likert scale (ranging from 1 to 7), that measure the impact of fatigue on daily functioning [21]. A person’s mean score indicates his/her level of fatigue. The following mean cut-off values were used: ≤4 indicates low fatigue, >4 and <5 indicates borderline fatigue, and ≥5 indicates moderate to severe fatigue [20]. We dichotomised into low fatigue (i.e. FSS <5) and moderate to severe fatigue (i.e. FSS ≥5).

A pain questionnaire with numeric rating scales from 0 (“no pain”) to 10 (“worst possible pain”) to indicate perceived pain intensity during activity and rest the previous week, was used [9]. The pain NRS has become the most widely used instrument for pain screening [22].

SCI and GP data

HADS results among adults with traumatic SCI (n = 153) were derived from the study by Lidal et al. (in Table 3) [23]. The SCI group had a mean age of 50.4 (SD 9.5), and with a higher proportion of males; 82 vs. 40% in the SB population in the current study. HADS results among the Norwegian GP (n = 40 646) were collected from the Nord-Trøndelag Health Study (The HUNT Study 4 Databank) [24]. The HUNT Study is one of the largest and most comprehensive health studies performed collected during four consecutive studies every decade since the mid 80-ies. The HUNT Study 4 took place between 2017 and 2019 and had more than 56 000 participants (54% response rate) [25].

None of the groups (SCI and GP) were matched to the current study group with respect to age or gender.

Statistical analyses

Descriptive analyses were performed, and absolute numbers (n) and percentages (%) are given. Due to the small sample size and lack of normal distribution for many variables, we applied non-parametric tests, namely, the Mann–Whitney U test for continuous variables and the Fisher’s exact test to compare categorical variables. Spearman correlation analyses were used to investigate the associations between the HADS and FSS results and the following variables: age, years of education, SB severity composite score, BMI, pain (NRS), perceived impact (NRS) of urine leakage or bowel incontinence on everyday life, and age when deterioration in gait function started. The correlation coefficients were reported as Spearmans Rho’s (r_s) along with p-values, and assessed as a strong (r_s > ±0.6), moderate (r_s ±0.6 to ±0.4), or weak (r_s < ±0.4) correlation. Differences in the HADS and FSS scores between the SB study group and (a) adults with SCI and (b) the GP, were analysed with independent samples t-tests. The effect sizes (ESs) were calculated using Cohen’s d, defined as the difference between the two means divided by the standard deviation (SD) corresponding to the largest comparison group. The ES levels were interpreted as small (0.20), medium (0.50) and large (0.80) [26,27]. For the presentation of the study group (Table 1), we used the dichotomised FSS as described above. A missing value analysis program was not used because <1% of the data were missing and no patterns related to the nature of the missing data were found. A p-value of <0.05 was considered statistically significant. All analyses were carried out using SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA).

Table 1. Characteristics of persons according to hydrocephalus status and according to fatigue status; dichotomized into low fatigue with FSS score below 5, or moderate to severe fatigue with FSS score 5 or above.

	Without hydrocephalus		With hydrocephalus
	n = 24		n = 6
	Low fatigue symptoms FSS score <5 n = 15	Moderate/severe fatigue FSS score ≥ 5 n = 9	Low fatigue symptoms FSS score <5 n = 3	Moderate/severe fatigue FSS score ≥ 5 n = 3
Gender, male; n (%)	7 (47)	2 (22)	1 (33)	2 (66)
Age (years) at follow-up; mean (SD), median; range	58.8 (6.0); 58; 51–76	58.0 (5.5), 56; 53–70	53.0 (2.0), 53.0; 51–55	56.5 (5.0), 56.5; 53–60
Employed at follow-up; n (%)	9 (60)	3 (33)	1 (33)	3 (100)
Years of education; mean (SD), median; range	14.3 (3.9), 14; 9–23	13.2 (3.7), 14; 8–19	14.0 (3.6), 13.0; 11–18	14.0 (1.4), 14.0; 13–15
Married or cohabitant at follow-up; n (%)	3 (20)	4 (44)	–	–
Spina bifida severity score (4–10); mean (SD), median; range	6.4 (1.3), 7.0; 4–8	7.2 (1.4), 7.0; 5–9	9.0 (0.0), 9.0	8.0 (1.7), 9.0; 6–9
BMI; mean (SD), median; range	25.2 (1.2), 25; 24–26	32.2 (11.4), 28; 22–58	35.8 (15.6), 22–53	34.2 (0.6), 34–35
Perceived impact of urine leakage (NRS); mean (SD), median; range	5.5 (3.5), 5.5; 3–8	2.50 (3.5), 2.5; 0–5	4.0 (1.0); 3–5	7.7 (3.5); 5–10
Perceived impact of bowel incontinence (NRS); mean (SD), median; range	5.0 (1.4), 5; 4–6	4.0 (5.7), 4.0; 0–8	3.7 (15.6); 3–5	7.7 (2.5); 5–10
Medication with possible fatigue or asthenia as side effect; n (%)
No such medication	7 (47)	–	–	1 (33)
One medication	3 (20)	3 (33)	–	2 (66)
Two medications	4 (27)	–	–	–
>Two medications	1 (7)	6 (67)	3 (100)	–
BMI mean (SD)	28.06 (5.4)	32.17 (11.4)	35.77 (15.6)	34.15 (0.6)*
Obesity (BMI ≥ 30)	6 (40)	3 (33)	2 (66)	2 (66)*
HADS total; mean (SD), median; range	6.3 (4.1), 6.0; 0–14	14.3 (5.6), 12.0; 7–22	13.7 (8.6), 12.0; 6–23	10.7 (4.5), 11.0; 6–15
HADS-A; mean (SD), median; range	3.9 (2.7), 4.0; 0–9	7.9 (3.9), 5.0; 4–14	9.0 (4.0), 5.0; 5–13	4.0 (4.2), 4.0; 1–7
Clinically relevant symptoms of anxiety (HADS-A > 8); n (%)	2 (13)	4 (44)	2 (66)	1 (33)
HADS-D; mean (SD), median; range	2.3 (2.3), 1.0; 0–8	6.4 (2.4), 6.0; 2–10	4.7 (4.7), 3.0; 1–10	6.5 (2.1), 6.5; 5–8
Clinically relevant symptoms of depression (HADS-D > 8); n (%)	1 (7)	3 (33)	1	1 (33)
Pain the past week (NRS 0–10); mean (SD), median; range	4.23 (2.59), 4.0; 0–8	6.22 (2.59), 6.0; 3–10	5.0 (1.0), 5.0; 4–6	3.5 (0.71), 3.5; 3–4
Pain during rest (NRS 0–10); mean (SD), median; range	3.1 (2.9), 3.0; 0–9	4.7 (2.7), 4.0; 1–10	4.3 (0.58), 4.0; 4–5	2.0 (0.00), 2.0; 2–2
Pain during activity (NRS 0–10); mean (SD), median; range	4.2 (2.3), 4.0; 0–8	6.4 (2.8), 7.0; 1–10	5.7 (0.57), 6.0; 5–6	5.5 (3.5), 5.5; 3–8
Compared to a year ago, how is your health today?* (RAND-36)
Much better	2 (13)	–	–	–
Fairly better	1 (7)	3 (33)	1 (33)	–
About the same	5 (33)	3 (33)	–	1 (33)
Worse	7 (47)	2 (22)	1 (33)	1 (33)
Much worse	–	1 (11)	–	1 (33)
How would you rate your health today?* (RAND-36)
Very good	7 (47)	1 (11)	–	–
Good	5 (33)	–	1 (33)	1 (33)
Fairly good	2 (13)	4 (44)	1 (33)	2 (66)
Poor	1 (7)	4 (44)	–	–

BMI: body mass index (kg/m²); FSS: Fatigue Severity Scale; HADS: Hospital Anxiety and Depression Scale (-A: anxiety subscale; -D: depression subscale); NRS: numeric rating scale; SB: spina bifida; SD: standard deviation.

*1 missing among those with hydrocephalus.

Estimation of number of persons with SB 50 years or older in Norway

We calculated our coverage of the target population by estimating the total number of Norwegian persons with SB born before 1967. The Medical Birth Registry of Norway is a national registry containing information on all births in Norway from 1967 onwards, and it includes the incidence of specific congenital abnormalities. According to the registry, the yearly incidence of live new-borns with SB in each of the years 1967–1970 was 31 on average, equalling eight per million inhabitants [28]. Based on this, we might assume that the number of new-borns with SB for each year before 1967 was approximately the same as the number born in each of the years 1967–1970. For the period 1930–1966, this gives us about 1085 new-borns with SB with or without hydrocephalus. Since treatment for significant hydrocephalus was established about 1960, we assumed that most of those born with hydrocephalus (i.e. 80% of all children with SB) died at a young age before 1960, but we did not manage to obtain documentation on this [29]. Assuming all of the above, the number of persons with SB aged 50+ who were alive in Norway in 2016 is likely <100. This means that the study group of 30 persons with SB probably represented about a third of the total SB population in these age groups.

Results

Sociodemographic and medical characteristics

In total, 30 middle-aged and older Caucasian adults with SB were studied; 18 women and 12 men. Their characteristics are shown in Table 1 and were extensively described in a previous paper as well [9]. The level of the defect was lumbar in 17 persons, sacral in 12, and thoracic in one. The defect was closed within the first day after birth in 14 persons and later (1–3 months after birth) in 11 persons with myelomeningocele. One person had skin-covered myelomeningocele that never had needed surgery. Four persons in our study group did not have myelomeningocele, but were born with other types of skin-covered SB (three with lipomyelocele and one unknown type). All four of them had neurological deficits, three had tethered cord while one was uncertain about tethered cord status—and all four reported symptoms of neuropathic pain and had affected urinary/bowel functions. Twenty-four (80%) persons did not have associated hydrocephalus. Five of the six persons with hydrocephalus were born after 1961 and had each a shunt, while one was born during the 1950s and did not have a shunt.

Psychological distress and fatigue outcomes

The FSS results showed that 13 (43%) persons had low fatigue, five (17%) persons had borderline fatigue, while 12 (40%) persons (eight women and four men) had moderate to severe fatigue (Table 1). Persons found to have moderate to severe fatigue were about the same age as those with lower fatigue scores; nine of them had hydrocephalus, and three did not. The mean (SD) FSS score for the total sample was 4.39 (1.39) and ranged from 1.56 to 6.67. The FSS mean difference compared to a national representative sample was 0.41, 95% CI, −0.0632–0.8832 (Cohen’s d = 0.30) [20]. The FSS scores were not correlated with age, SB severity composite score, years of education, BMI, age when walking ability started to decrease, or degree of perceived impact of urine leakage or bowel incontinence on everyday life. The FSS scores were moderately correlated to the reported intensity of pain during activity (r_s = 0.423, n = 30, p = 0.02). Eleven out of 12 persons who scored to have moderate to severe fatigue used prescribed drugs with known possible fatigue or asthenia side effect. The most common medications were antihypertensive drugs, analgesics, and medications prescribed to reduce spasticity problems. The overall subjective health assessments showed that 72% of persons with low fatigue scores rated their health as very good or good, while among those whose score indicated moderate to severe fatigue, 83% rated their health as fair or poor. Forty-three percent of the study population rated their current health as worse or much worse than a year ago (Table 1).

Table 2 shows the HADS results for the studied SB group, and also the scores available for the GP and middle-aged and older adults with chronic SCI [23,24]. The SB group had higher scores on all subscales, indicating more symptoms of psychological distress than the GP and the calculated ESs were small to medium, indicating small clinical differences in the SB group compared to the GP. Furthermore, statistically significant differences were observed between persons with SB and adults with chronic SCI. Persons with SB reported a higher symptom prevalence of psychological distress (HADS-T), depression (HADS-D), and anxiety (HADS-A), p’s < 0.001 with medium to large ESs. Only one person had a follow-up by a psychologist, there were no follow-ups with a psychiatrist. Two persons used daily medication for depression. Nine persons (30%) scored above the threshold for clinically relevant anxiety, while six (20%) scored above the threshold for clinically relevant depression. The mean (SD) HADS-T score was 9.9 (6.1) with a range of 0–23, the mean (SD) HADS-A score was 5.8 (3.8) with a range of 0–14, and the mean (SD) HADS-D score was 4.0 (3.1) with a range of 0–10. The HADS scores did not differ significantly between genders. The HADS scores were not correlated with the following variables: age, SB severity composite score, years of education, BMI, perceived impact of urine leakage on everyday life, or perceived impact of bowel incontinence on everyday life. The HADS-T and HADS-D scores correlated with pain results (r_s = 0.458, n = 30, p = 0.026; and r_s = 0.439, n = 30, p = 0.015, respectively). Furthermore, the HADS-T and HADS-D scores correlated with the FSS scores (r_s = 0.423, n = 30, p = 0.02; and r_s = 0.459, n = 30, p = 0.011, respectively). The correlation coefficients above indicate moderate correlations.

Table 2. HADS results in the SB-population (n = 30) compared to (1) mean expected scores (n = 40 646)* and (2) mean scores in an ageing spinal cord population (n = 153)**.

	SB mean (SD)	Expected mean (SD)*	Mean difference	95% CI	p-Value	Effect size
HADS-T	9.87 (6.13)	7.68 (5.66)	−2.19	−4.22 to −0.16	0.034	0.39
HADS-A	5.8 (3.82)	4.40 (3.46)	−1.40	−2.64 to −0.16	0.0265	0.40
HADS-D	4.0 (3.16)	3.30 (2.96)	−0.70	−1.76 to 0.36	0.195	0.24
	SB mean (SD)	SCI mean (SD)**	Mean difference	95% CI	p-Value	Effect size
HADS-T	9.87 (6.13)	5.8 (5.02)	−4.07	−6.12 to −2.02	0.0001	0.78
HADS-A	5.8 (3.82)	3.60 (3.20)	−2.20	−3.50 to −0.90	0.001	0.67
HADS-D	4.0 (3.16)	2.20 (2.60)	−1.80	−2.86 to −0.73	0.001	0.67

CI: confidence interval; SD: standard deviation; SB: spina bifida; SCI: spinal cord injury; HADS: Hospital Anxiety and Depression Scale (-A: anxiety subscale; -D: depression subscale; T: total scale).

Effect size: Hedges’ g.

*Derived from HUNT 4 (https://hunt-db.medisin.ntnu.no/hunt-db/#/variable/7259) (sample size HADS total: n = 40 646; HADS-A: n = 41 131; HADS-D: n = 41 440).

**Derived from Lidal et al. (n = 156) [21].

Discussion

To our knowledge, this is the first study to address depression, anxiety, and fatigue symptomatology in persons with SB aged 50 years or older. These are the main findings: The study population had significantly higher HADS scores compared to the GP and adults with chronic (>20 years duration) SCI. In total eleven persons (36%) scored above the thresholds for clinically relevant anxiety or depression. However, few of these persons reported receiving any kind of follow-up; one person had follow-up by a psychologist, one person had followed up by a psychiatric nurse, while none reported using antidepressant medications. The results also indicated a high rate of moderate to severe fatigue, and fatigue seemed to be associated with the use of medications that have possible fatigue or asthenia side effects. The HADS-D and FSS scores were correlated, and both variables were also correlated with pain intensity experienced the past week.

Although the study sample was small, we assume that the results are generalizable to Norwegian persons with SB with neurological deficits born before 1967. There is, however, a risk that we have studied healthier persons with a lower degree of SB disability. Our previously presented results indirectly indicated a generally high-functioning SB study group in terms of physical functioning and participation [9]. If so, we might have underestimated results on health issues, such as the perceived impact of urine and/or bowel incontinence, pain problems, and medication usage—and thus probably the results on fatigue among middle-aged and older adults with SB, as well. The results presented separately for those without hydrocephalus (n = 26), are also relevant to adults with SB without hydrocephalus born after 1967. The low proportion (20%) with hydrocephalus in the studied population was explained by low survival with untreated significant hydrocephalus in persons with SB born before 1960. The prevalence of hydrocephalus is much higher in younger adults living with SB myelomeningocele, today [8]. It is possible that younger adults have the same or worse figures of psychological distress and fatigue symptomatology than demonstrated in this study group, but this needs to be evaluated in future studies.

According to existing literature (2010–2021), no studies investigated fatigue in adults with SB, while eight publications reported on psychological distress in adults with SB (Table 3); two randomised controlled trials (RCTs) [30,31] and six observational studies [32–38]. The studies were conducted in North America (n = 4) [32,33,36–38], Australia (n = 2) [30,34] and Europe (n = 2) [31,35]. The mean age of the participants ranged from 21 to 41 years old, and the gender distribution skewed towards females in all studies except for one [35]. Most studies did not present results for different types of SB subgroups separately. One study selected persons with SB with “problematic psychosocial issues” [35], another recruited persons from patient organizations and support groups [34], while another study recruited participants through Facebook users who “liked” or were members of Facebook pages related to the Spina Bifida Association [37,38]. One study explored a broad range of experiences with chronic neurological conditions in a population-based sample [36]. Three studies recruited persons with SB from tertiary SB clinics [30,32,33] and one study from a national resource center for rare disorders [31]. Measurement tools used were The Hopkins Symptom Checklist (HSCL-25), Beck Depression Inventory-II (BDI-II), Depression, Anxiety and Stress Scales-21 item (DASS-21), The Symptom Checklist 90-R, The Patient Health Questionnaire [Brief Patient Health Questionnaire, 9-item (PHQ-9)], The Patient-Reported Outcome Measures Information System (PROMIS) instruments (Depression 8a Short Form v1.0, Anxiety 8a Short Form v1.0, and Social Isolation 6a Short Form v2.0, respectively). Proportions with anxiety symptomatology ranged from 17 to 47%, and depression symptomatology ranged from 19 to 48% in these very heterogeneous studies (aims, design, populations, and measurement tools). The current study is added to Table 3 for comparison. Interpretations of results from the studies have not been included in the current paper, and need to be understood in conjunction with possible research biases judged with critical appraisal tools according to study design; casp-uk.net. Therefore, we suggest a systematic review to be conducted.

Table 3. Characteristics of studies (2010–2020) measuring psychological distress in adults with SB.

Author; year; country of origin	Title	Design	Aim	Methods	Population and SB characteristics	Psychological measurements; rates (prevalence) of symptoms
Bellin MH, 2010; US [32]	Correlates of depressive and anxiety symptoms in young adults with SB	Longitudinal: The current study presents the first data (Time 1) on psychological functioning	Based on social ecological theory, this study was designed to examine the unique relationships between multi-level ecological factors and psychological symptoms in young adults with SB	Standardized self-report measures of attitude toward SB, satisfaction with family functioning, Chronic Care Model (CCM) services, and depressive and anxiety symptoms. A chart review yielded SB clinical data	n = 61 with SB; 60.7% females Mean age 21.05 y (SD:2.11) 18–25 y Level of SB; Th:13.1%, L: 55.7%, S:31.1% Hc: 68.9% Study setting: Recruited from five geographically diverse SB clinic sites	The Hopkins Symptom Checklist (HSCL-25) was administered as a self-report index of depressive and anxiety symptoms. 41% scored in the range of clinical depression; 31.1% scored above the cut-off for anxiety symptoms.
Bulloch AGM; 2015; Canada [36]	Depression—a common disorder across a broad spectrum of neurological conditions: a cross-sectional nationally representative survey	Cross-sectional study	To establish the prevalence of depression across a range of neurological conditions in the general population, using the same sampling and assessment methods and using data drawn from the Survey of Living with Neurological Conditions in Canada (SLNCC)	The authors estimated both crude as well as age and sex adjusted ORs of depression in each condition with the baseline group being the general population of the CCHS sample	n = (not reported specifically for SB); The final sample for the SLNCC analysis included 4400 persons and included a range from 110 to 730 persons with rare conditions. Not given the exact number of persons with SB; 61.7% SB females Mean age 38.8 (CI: 33.7–43.9) y; 16–79 y Level of SB: not reported Hc: not reported Study setting: The data source was the SLNCC, which accrued its sample by selecting people from the Canadian Community Health Survey.	The Patient Health Questionnaire, Brief Patient Health Questionnaire, 9-item (PHQ-9). The estimated prevalence of depression was 18.6 (CI: 9.1–28.0). The odds ratios for depression, with the referent group being the general population, was non-significant for SB.
Dicianno BE, 2015; US [33]	Depressive symptoms in adults with SB	Retrospective cohort study	To examine the prevalence of depressive symptoms in adults with SB and identify contributing factors for depressive symptomatology	Charts from adult persons with SB; The main outcome measures were the Beck Depression Inventory-II (BDI-II) and the mobility domain of the Craig Handicap Assessment Reporting Technique Short Form (CHARTSF)	n = 190 with SB; 54.3% female; primary diagnosis of SB cystica or occult with an underlying neurological abnormality Mean age 33.6 (SD: 11.1) y, median 31.0 y (range 18–77) Level of SB: Th: 18.9%, L: 69.9%, S: 7.9% Hc: Not reported Study setting: Data collection at a regional adult SB clinic	Beck Depression Inventory-II (BDI-II) 25.8% scored to have depressive symptoms
Hayter MR and Dorstyn DS, 2014; Australia [34]	Resilience, self-esteem and self-compassion in adults with SB	Cross-sectional survey	To investigate the characteristics of resilience in a community sample with SB, including the impact of disability severity on resilience levels and the association between resilient skills and behaviours and psychological functioning	Online survey	n = 97 with SB; 66% females; meningocele, myelomeningocele or myeloschisis, with and without associated Hc Mean age: 40.1 y (SD 11.8); median 39.5, range 19–73 y Level of SB: Not reported Hc: 57.7% Study setting: Online data collection through community-based disability organisations/SB support groups	Depression, Anxiety and Stress Scales—21 item (DASS-21). 21.6%, 22.7%, and/or 15.55 were cases with severe to extremely severe levels of depression, anxiety, and/or stress, respectively
Khan F; 2015; Australia [30]	Rehabilitation outcomes in persons with SB: a randomised controlled trial	RCT	To assess the effectiveness of an interdisciplinary ambulatory rehabilitation programme for persons with SB in an Australian community cohort	Included persons were randomized to a treatment group for a high-intensity rehabilitation programme (with cognitive behavioural therapy) or a control group comprising usual care	n = 54; n = 27 in intervention group (66.7% females) and n = 27 in control group (48.1% females). Diagnosis of SB (clinical and radiological) Mean age 32.9 (SD: 9.2) y Level of SB: Intervention group: L2 21.7%, L3–5 69.6%, <S1 4.3%; Control group: L2 14.3%, L3–5 47.6%, <S1 33.3% Hc: Intervention group 57.7%, controls 68.0% Study setting: The treatment group received an individualized high-intensity rehabilitation programme at a regional SB clinic. The control group received standard care at home and were reviewed in the SB clinic at 6-monthly intervals	Depression, Anxiety Stress Scale (DASS), McGill Quality of Life (MQOL), Brief COPE Scale, Generalized Self-efficacy Scale (GSE) At 3 months post-intervention, significantly improvements were found for depression, anxiety and stress subscales of DASS compared to controls.
Showen A, 2021; US [37, 38]	Characteristics associated with depression, anxiety, and social isolation in adults with spina bifida	Cross-sectional study	To identify demographic and clinical characteristics associated with depression, anxiety, and social isolation among adults with spina bifida	A survey distributed via Facebook advertising to individuals with congenital urologic conditions. Adults with spina bifida were included. The primary outcomes of depression, anxiety, and social isolation were measured using Patient-Reported Outcome Measures Information System (PROMIS) instruments (Depression 8a Short Form v1.0, Anxiety 8a Short Form v1.0, and Social Isolation 6a Short Form v2.0, respectively)	n = 195 with SB; 74.9% female; diagnosis of SB Mean age 40.2 (SD: 12.6) y, (range 18–72) Level of SB: not reported Hc: 44.6% with ventriculoperitoneal shunt Study setting: Recruitment through Facebook users who “liked” or were members of Facebook pages related to the Spina Bifida Association.	The mean depression score was 55.3 (SD 10.6). In total 48% with depression: 14% with mild, 29% with moderate, and 5% with severe depression. The mean depression score differed significantly from a mean score of 50 (SD 10) for a US general population sample (p < 0.001). The mean anxiety score was 55.0 (SD 11.7). In total, 47% with anxiety: 12% with mild, 28% with moderate, and 7% with severe anxiety. The mean anxiety score differed significantly from a mean score of 50 (SD 10) for a US general population sample (p < 0.001).
Stubberud J, 2015; Norway [31]	Emotional health and coping in SB after goal management training: A randomized controlled trial	RCT	The purpose was to determine the efficacy of GMT on aspects of perceived emotional health and coping in persons with SB.	Experimental subjects received 21 h of GMT, with efficacy of GMT being compared with results of subjects in a wait-list condition. Four self-report questionnaires assessing emotional health and coping were utilized as outcome measures. All subjects were assessed at baseline, post-intervention, and at 6-month follow-up	n = 38 MMC; Intervention n = 24 and control group n = 14. 58% females (not statistically different between intervention- and controls Mean age: 32 (SD: 8.3) y (range 19–45 y) [not statistically different between intervention- and controls: intervention: 31.8 (8.4) y; controls: 31.8 (SD: 8.5) y]; Level of SB: Th: 5%; L: 89%; S: 5% (not significantly different between intervention- and control group) Hc: 87% (intervention: 88%; controls: 86%) Study setting: Outpatient clinic	Hopkins Symptom Checklist 25 (HSCL-25, is a 25-point self-report inventory of depressive and anxiety symptoms. A significant reduction in the presence and intensity of total anxiety and depression symptoms for the GMT group compared to controls at 6 months follow-up.
Stubberud J and Riemer G, 2012; Norway [35]	Problematic psychosocial adaptation and executive dysfunction in women and men with MMC	Cross-sectional study	To characterize women and men with problematic psychosocial adaptation with respect to cognitive functions and psychological symptoms	Between Jan. 2007 and Dec. 2008, 65 persons between the age of 18 and 45 y (40 women, 25 men) contacted TRS because of various medical and psychosocial reasons: inclusion criteria were: (1) Uncompleted upper secondary; (2) Unemployment the last 3 y; (3) Lack of social relationships (e.g., living alone, absence of close friends, deficiency to engage in any form of play, recreational or leisure activity). The included persons with SB underwent 2 h neuropsychological assessment	n = 12; 50% females Mean age: 32 y (SD: 5.7) (range 24–41 y) Level of SB; Th10-S1 Hc: 92% Study setting: Outpatient clinic	The Symptom Checklist 90-R was used to document self-reported psychological problems and symptoms of psychopathology. 25% (n = 3) and 17% (n = 2) scored above the cut off level for depression and/or anxiety, respectively.
Lidal and Lundberg Larsen 2020; Norway (Current paper)	Anxiety, depression and fatigue in middle-aged and older persons with SB: A cross-sectional study and a systematic scoping review	Cross-sectional survey	To assess the prevalence of anxiety, depression and fatigue in a SB population aged 50+, and to systematically review publications on psychological health in adults with SB	Data collected face-to-face from thirty home-dwelling persons with SB ∼ 30% of the total SB-50+ population in Norway, in 2018. Predefined fixed questionnaires on SB-specific issues, the Hospital Anxiety and Depression Scale (HADS) and the Fatigue Severity Scale (FSS) were used.	n = 30 with SB; 60% female Mean age: 57.5 y (SD 5.6) range 51–76 y Level of SB; Th 3%, L:57%, S:40% Hc: 20% Study setting: Outpatient clinic at a National resource centre	The Hospital Anxiety and Depression Scale (HADS) was used. HADS-depression subscale scores showed that 20% scored to have depression, while the HADS-anxiety subscale showed that 30% scored to have anxiety

CCHS: Canadian Community Health Survey; Hc: hydrocephalus; L: lumbar; MMC: myelomeningocele; S: sacral; SB: spina bifida; SD: standard deviation; SBSC: the spina bifida secondary conditions survey tool; Th: thoracic; Uk: unknown; Y: years.

Recently published mental health guidelines suggest screening for anxiety and depression during SB follow-ups [39]. It is unclear which clinical measurement tools that are preferable as screening methods for psychological distress symptoms among adults with SB. The overview of studies (Table 3) revealed that several tools have been applied, but to our knowledge, none have been specifically recommended for the evaluation of psychological distress among adults with SB. The HADS was chosen in this study, because it is validated in the Norwegian GP, and also used in the HUNT and studies of Norwegians with SCI [18,19]. The results in this particular group of middle-aged and older adults with SB, indicated a symptom prevalence of anxiety (30%) and depression (20%) in the same range as found in other studies of SB using other tools (Table 3) [30–32,34–36]—although these studies were mostly of younger adults, with a higher prevalence of hydrocephalus, and with different aims than ours. We could not find publications of a similar age group as in the current study, although persons with SB between 18 and 72 years were included in a Facebook survey [37,38].

One study of young adults with SB used the HSCL-25 as a self-report index for anxiety and depressive symptoms and found pain to be correlated with symptoms of anxiety [32], while our study indicated that pain correlated with HADS-D. Moreover, pain was the main health complaint among long-term survivors after SCI [23] as also found in this SB population [9], however, our sample size was too small to study the relationships between pain, psychological distress, and fatigue symptoms. Maybe regular screening of pain in persons with SB can help identify those at risk for psychological distress symptomatology [39]?

Interestingly, the perceived impact of urine leakage and the perceived impact of bowel incontinence on everyday life in this study population were not correlated with HADS scores. Liu et al. demonstrated a close correlation between urinary incontinence–related and general health quality of life, suggesting that incontinence plays a significant role in perception and satisfaction with general health in adult persons with SB [40]. Their number of persons reporting faecal incontinence was very small (6%). Our previous paper on the current study population showed that 40% avoided certain daily tasks due to faecal incontinence, including social settings, transportation, and physical activities [9].

A high proportion (40%) of the study population reported moderate to severe fatigue. Those with moderate to severe fatigue symptomatology reported fairly good or poor health, which might be interpreted as an indication of a high symptom burden. Fatigue prevalence has been estimated to be about 22% in the Norwegian GP (measured with FSS) and 25% among middle-aged and older adults with chronic SCI (measured with the Fatigue Questionnaire) [20,23]. Pain scores were also associated with fatigue in the SB population in accordance with findings in the GP and among persons with SCI [9,23]. Based on the known complexity and associated secondary conditions in persons with SB, there are also many comparable challenges with persons with CP. We found a higher prevalence of moderate to severe fatigue symptomatology (40%) in the study group compared with adults with CP (30%) [41]. Jahnsen et al. [41] used the Fatigue Questionnaire and found a significant difference in CP from the reference group only for physical fatigue, but not for mental fatigue. The authors were surprised because mental fatigue addresses cognitive aspects, such as concentration and memory, which are common among persons with CP. Their study also showed that the strongest predictors associated with fatigue were bodily pain, deterioration of functional skills, limitations in emotional and physical role function, and low life satisfaction [41]. The FSS used in the current study could not differentiate mental and physical fatigue. As studies of CP also recommend lifestyle interventions, such as weight management and physical activity, to prevent and treat fatigue, this should be explored in studies of persons with SB, as well [42]. Furthermore, nutrition is essential for vitality, and known to impact psychological distress and fatigue symptomatology, and should therefore be taken into account when evaluating possible risks and protective factors for fatigue [43,44].

All persons identified with moderate to severe fatigue in this study, used medications with possible fatigue side effects, while only half of those with low fatigue symptomatology used such medications. Meanwhile, although fatigue is listed as a medication side effect, RCTs may reveal whether persons are experiencing a genuine side effect from the drug since the fatigue findings might be caused by medications, the neurological condition itself, or another coincident problem. For this study population, we think the nocebo phenomenon is a minor factor because the medications had probably been used for years by most of the included persons with SB. Other important factors to be considered in relation to fatigue symptomatology are anaemia, physical deconditioning, respiratory dysfunction, and sleep disorders.

To study a mixed SB population with regard to SB severity is not optimal. We solved this by presenting the results for the six persons with SB with hydrocephalus separately. The four persons born with skin covered SB with neurological deficits were studied along with the 20 persons with myelomeningocele without hydrocephalus. Still, the two conditions (skin-covered SB and myelomeningocele) differ with regard to severity.

Studies should explore interventions aimed at preventing and reducing fatigue symptoms in adults with SB, and further clarification of the role of psychological distress and pain should be documented. If introducing screenings and interventions for fatigue or psychological distress symptomatology as part of follow-up programs, the effects should be evaluated.

Strengths and limitations

The main strength of this cross-sectional study was the use of validated measurement tools: HADS, FSS, and the NRS for pain. The fidelity of the questionnaires should be better tested in future studies. We think that fatigue assessment tools that distinguish between mental and physical fatigue probably should be recommended for future research of persons with SB. Another strength was that a few data were missing. The recruitment was conducted broadly [9] and covered about 30% of middle-aged and older persons living with SB in Norway. However, we studied long-term survivors with SB, and therefore our study population represented a selected group. There is a risk that the study sample may be underpowered and skewed towards healthier persons. In future studies with a higher number of participants, authors might consider latent class analysis for determining subgroup characteristics of those that are most at risk for their measured outcomes of psychological distress, fatigue, etc. For example, given the associations we discovered with pain, pain ratings/profile or use of pain medications might be a good clinical indicator for referrals to mental health services or other services that address fatigue.

Concerning the data collected, some questions may have introduced recall bias, such as the open-ended question about current medication usage. Another limitation is that we did not collect information on nutrition, which is specifically important when it comes both to psychological distress and fatigue symptomatology. We want to underline that the use of BMI in this population is challenging because of the effect of the abnormality on linear growth.

Conclusion

In line with the proportions found in other studies, 30 and 20% of the studied persons with SB scored above the HADS-A and HADS-D thresholds, respectively; however, few of them received any form of therapy for psychological distress. The proportion with psychological distress symptomatology was higher in the Norwegian SB group compared to the GP and compared to chronic SCI. Moderate to severe fatigue symptoms were common among Norwegian adults aged 50 years old or older with SB. Still, we did not identify any other relevant studies on fatigue in adults with SB for the reviewed period 2010–2021. Future studies should aim to identify risks and protective factors and treatment strategies for fatigue, and also to further evaluate methods for detecting and monitoring psychological distress in persons with SB. We suggest that SB follow-ups of adult persons with SB should include awareness of depression, anxiety, and fatigue symptomatology.

Author contributions

Both I.B.L. and K.L.L were jointly responsible for the protocol and design, data collection, analyses, and interpretations. I.B.L. was mainly responsible for writing the manuscript. Both authors searched for relevant literature and agreed upon the documentation presented in Table 3.

Ethical approval

We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research.

Acknowledgements

We want to thank The Norwegian Association for Spina Bifida and Hydrocephalus for advice during the planning of the study. A special thanks to our colleague Marie Hoff for being a part of the research team. We also want to thank Jan Erik Wilhelmsen for helping with the literature search, Trine Bathen and Elisabeth Fagereng for reading and commenting on our article.

Disclosure statement

The authors declare to have no conflict of interest.

Data availability statement

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.