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Correspondence to: Liesbeth de Wall, Department of Urology, Division of Paediatric Urology, Radboud University Medical Center, Amalia Children's Hospital, Geert Grooteplein Zuid 10, Nijmegen, 6500 HB, the Netherlands, Tel.: +31 24 3613735; fax: +31 24 3635114
Lower urinary tract dysfunction (LUTD) in childhood might affect lower urinary tract function and psychological wellbeing later in life. This study presents long-term functional outcome, psychological outcome and quality of life (QOL) of adolescents and young adults treated for childhood LUTD compared to healthy age-matched controls. In addition, association with past treatment outcomes is evaluated.
Study design
A single-centre cross-sectional study of former patients treated in childhood (currently 16–26 years old) was conducted. Participants completed a survey composed from validated questionnaires: the Overactive Bladder Questionnaire, the Hospital Anxiety and Depression Scale, the Pediatric Quality of Life Inventory and the Short Form 36 Health Survey.
Results
Fifty-two former patients (out of 133) agreed to participate and returned the survey (mean age 21 ± 4.1 years). Sixty-nine control subjects were included (mean age 21 ± 2.9 years). Urinary tract symptoms were more common in former patients than controls. Storage symptoms more frequently reported were (urge) urinary incontinence, stress urinary incontinence (SUI) and nocturia. Voiding symptoms more frequently reported were intermittency and feeling of incomplete emptying, Fig. 1. There were no differences in urinary tract symptoms or urinary incontinence subdivided by childhood treatment outcome (complete response, partial response or no response), respectively p = 0.17 and p = 0.58. Results of the overactive bladder questionnaire revealed higher urinary symptom bother scores (score 14 versus 5 p < 0.01) and lower disease-specific QOL (score 95 versus 98 p = 0.02) in former patients compared to controls. General QOL and psychosocial wellbeing were not significantly different between the two groups. A childhood treatment duration extending 2,5 years was an independent prognostic factor for subsequent urinary tract symptoms later in life (OR = 1.5, 95% CI 1.1–2.0). Psychological comorbidity was more often present in former patients (35%) versus controls (10%), p < 0.01.
Conclusion
Graphical AbstractLower urinary tract symptoms in the control group and former patient group - subdivided for treatment outcomes in complete, partial and no response; in accordance with the definitions and classifications by the International Children's Continence Society. ∗p < 0.05.
]. In young adults, the prevalence varies greatly between 2 and 53% depending on the selected population, type of urinary tract symptoms, severity and measurements used [
Childhood LUTD is associated with lowered self-image, lower quality of life (QOL) and a negative impact on psychosocial wellbeing at the time of occurrence [
]. Less is known about the effect on psychosocial wellbeing later in life even if actual treatment has ended years ago.
The association of childhood LUTD and urinary tract symptoms later in life remains an interesting topic. Data about the number and types of urinary tract symptoms in adolescents and young adults treated for functional childhood LUTD is scarce since children are lost to follow-up by their paediatricians/paediatric urologists upon reaching adulthood. Previous studies mainly include either middle-aged adults, in whom comorbidities might act as a confounder, or young females [
]. Less is known about the presence of urinary tract symptoms and QOL in, for example, young males or adolescents previously treated for LUTD.
The aim of this study is to determine the number, type, severity and impact of urinary tract symptoms in adolescents and young adults treated for childhood LUTD and to compare outcomes to those of healthy age-matched controls. Validated questionnaires are used to collect data about the presence of urinary tract symptoms, QOl and psychosocial wellbeing. An overall higher number of urinary tract symptoms and diminished QOL in former patients compared to healthy age-matched controls is hypothesized.
Material and methods
A single-centre cross-sectional study of all former patients with available and valid contact details – who were treated for functional LUTD in childhood in our tertiary clinic - was conducted. None of the subjects were under active follow-up at the time of the study. Subjects were asked via telephone to participate. Healthy controls were recruited by word of mouth and advertisement at the university faculty and high schools nearby. They were included only if absence of urological history was confirmed.
Inclusion & exclusion
Former patients treated for functional LUTD – currently aged between 16 and 26 years – were eligible for participation. Functional LUTD was defined according to the International Children's Continence Society (ICCS) and included overactive bladder (OAB) with or without UI, dysfunctional voiding and underactive bladder, all either with or without urinary tract infections (UTIs) [
The standardization of terminology of lower urinary tract function in children and adolescents: update report from the standardization committee of the International Children’s Continence Society.
]. Those with neurological conditions or anatomical anomalies were excluded. LUTD was assessed according to protocol with a detailed and structured history, a frequency voiding chart, thorough physical examination, urinalysis and uroflowmetry with post void residual measurement. Urodynamic studies were done if indicated.
Since 1996, two trained nurse specialists have provided treatment in our clinic according to an outpatient clinical protocol in line with current standardized documents [
Definitions, indications and practice of urotherapy in children and adolescents: - a standardization document of the International Children’s Continence Society (ICCS).
Urotherapy in children: quantitative measurements of daytime urinary incontinence before and after treatment according to the new definitions of the International Children’s Continence Society.
]. Since ICCS's definitions were first published in 2006, retrospective chart analyses was performed to determine the type of LUTD of all former patients, including those treated before 2006.
Former patients who agreed to participate were sent a four-part paper survey and informed consent form. The four-part paper survey included questions about demographics, psychological comorbidity, urinary tract symptoms, general and disease-specific QOL and psychosocial wellbeing/mental health.
In former patients, retrospective chart review was completed to determine presence of psychological conditions at the time of treatment in childhood, type and severity of LUTD, type and duration of treatment and response (resolution of symptoms and official response according to the ICCS criteria) [
The standardization of terminology of lower urinary tract function in children and adolescents: update report from the standardization committee of the International Children’s Continence Society.
]. Additional questions not covered by OAB-q regarding voiding symptoms like hesitancy, feeling of incomplete emptying, stress urinary incontinence (SUI), straining and UI severity were also included. The latter not as part of a validated instrument as this does not exists for adolescents or young adults of both genders in our language.
General QOL (PedsQOl/SF-36)
Either the Pediatric Quality of Life Inventory (PedsQOL) or Short Form 36 Health Survey (SF-36) were used to asses general QOL [
]. Since one instrument does not cover all age ranges, two different validated instruments were used: the PedsQOL for participants <18 years of age and the SF-36 for participants ≥18 years of age [
A power analysis with a hypothesized 25% more urinary tract symptoms in former patients than healthy controls (α = 0.05, β = 0.20) suggested a sample size of 120 participants in total. The study was approved by the local Research Ethics Committee (NL 64311.091.17) and registered in an accessible study registry (ISRCTN89818320). Demographics were expressed as numbers and proportions (mean ± standard deviation [SD] or median and range). An unpaired t-test or one-way ANOVA was performed for normally distributed continuous data, and a Mann–Whitney U test was used for non-normally distributed continuous data. A chi-square or Fisher's exact test was performed for binary and nominal data. The data were analysed using SPSS Statistics 25.0. Differences were considered statistically significant at p < 0.05.
A logistic model was generated to study predictive factors for urinary tract symptoms of former patient later in life. An OAB-q symptom bother score >22 was considered an appropriate cut-off point, representing significantly higher storage symptoms than to be expected in a healthy control group of the specific age group studied in this study [
]. Due to the lack of a single validated questionnaire (in our language encompassing both genders) for voiding symptoms in particular, the model only included storage symptoms.
A binary logistic regression model based on the value of independent predictors was generated. The possible prognostic factors included gender, psychological comorbidity, treatment duration, treatment outcome and age at end of treatment. Parameters with p values > 0.3 were removed from the univariate model. Finally, a multivariable backward model was executed in which treatment outcome, treatment duration and age ≥ or <12 at the end of treatment were included as variables.
Results
Medical data were available for 133 (out of 317) former patients with valid contact details who were 16 years of age or older at the time of the study. After being contacted, 86 initially agreed to participate, while seven declined (lack of interest or time) and 40 remained unreachable. A total of 52/86 former patients returned the survey. Sixty-nine subjects were enrolled as controls. Overall survey completion rate was 99%.
Demographics (age, gender, history of psychological comorbidity) of the former patients who returned the envelope were not significantly different from those who initially declined participation, remained unreachable or did not return the survey. The former patient group (N = 52) was considered representative of adolescents and young adults treated for childhood LUTD in a tertiary clinic.
Educational level, income and marital status differed significantly between former patients and healthy controls. A psychological history-mainly attention deficit disorder (ADHD) or autism-was present in 18/52 (35%) of former patients versus 7/69 (10%) of controls, p < 0.01, Table 1. Only three participants (one former patient and two controls) were under psychiatric care at the time of the study, the remaining had finished treatment more than 1 year before the study started.
Table 1Baseline characteristics of former patients and healthy age-matched controls.
Urinary tract symptoms in former patients and healthy controls
A higher overall symptom bother score – indicating more current urinary tract symptoms – was seen in former patients compared to controls, Table 2A/2B. At least one type of symptom - expressed as being present quite a bit, a great deal or a very great deal – was seen in 59% of former patients versus 19% of controls, p < 0.01.
Table 2AQuestions according to the Overactive Bladder Questionnaire (OAB-q) divided into symptom bother scores and disease-specific quality of life (Disease-specific QOL) score.
Former patients N = 52
Controls N = 69
p-value
Sum of symptom bother score (median and 25–75 quartiles)
14 (5–23)
5 (1–10)
<0.01
Questions OAB-q
Frequent urination
A little, somewhat
25 (48%)
23 (33%)
0.10
Quite a bit, a great deal, a very great deal
11 (21%)
7 (10%)
0.09
Uncomfortable urge to urinate
A little, somewhat
12 (23%)
10 (14%)
0.22
Quite a bit, a great deal, a very great deal
7 (13%)
4 (6%)
0.15
Sudden urge to urinate without warning
A little, somewhat
10 (19%)
10 (14%)
0.49
Quite a bit, a great deal, a very great deal
6 (12%)
3 (4%)
0.14
Accidental loss of small amounts of urine
A little, somewhat
18 (35%)
9 (13%)
< 0.001
Quite a bit, a great deal, a very great deal
4 (8%)
–
0.02
Nocturia
A little, somewhat
17 (33%)
26 (38%)
0.57
Quite a bit, a great deal, a very great deal
10 (19%)
2 (3%)
< 0.01
Waking up to urinate
A little, somewhat
17 (33%)
23 (33%)
0.94
Quite a bit, a great deal, a very great deal
12 (19%)
2 (3%)
<0.001
Uncontrollable urge to urinate
A little, somewhat
12 (23%)
14 (20%)
0.71
Quite a bit, a great deal, a very great deal
1 (2%)
1 (1%)
0.84
Urge urinary incontinence
A little, somewhat
11 (21%)
4 (6%)
0.01
Quite a bit, a great deal, a very great deal
2 (4%)
1 (1%)
0.42
Disease-specific QOL total score (mean ± SD)
95 ± 9.3
98 ± 4.1
0.02
Coping
97 ± 11.1
99 ± 4.5
0.23
Concern/worry
93 ± 12.5
99 ± 4.3
0.01
Sleep
93 ± 13.3
96 ± 7.4
0.09
Social interaction
98 ± 5.4
100 ± 2.9
0.04
Symptom bother scores range from 0 to 100, higher scores indicate more urinary tract symptoms. Disease-specific QOL range from 0 to 100. Lower Disease-specific QOL scores indicate a more affected Disease-specific QOL. Bold value indicates p < 0.01.
Both storage and voiding symptoms were significantly more frequently reported by former patients than by controls, Summary Figure, Fig. 1. Storage symptoms more frequently reported were (urge) urinary incontinence, SUI and nocturia. Voiding symptoms more frequently reported were intermittency and feeling of incomplete emptying. Daytime UI was reported by 41% of former patients and 10% of controls, p < 0.01.
Fig. 1Lower urinary tract symptoms in the control group and former patient group subdivided for treatment outcomes (complete, partial and no response; in accordance with the definitions and classifications by the International Children's Continence Society) ∗p < 0.05.
Disease-specific QOL in former patients and healthy controls
Overall disease-specific QOL score was 95 ± 9.3 in former patients versus 98 ± 4.1 in controls, p = 0.02. The subscales concern/worry and subscale social interaction were significantly lower in former patients (i.e., more worries and concerns and less social interaction). Other subscale scores were not significantly different, Table 2A.
QOL and psychosocial wellbeing/mental health in former patients and healthy controls
General QOL (PedsQOL and SF-36) and psychosocial wellbeing (HADS) were not significantly different between the groups (Table 3A and 3B).
Table 3AGeneral quality of life scores.
Patients N = 52
Controls N = 69
p-value
QOL < 18 years (PedsQOL; mean ± SD)
N = 26
N = 22
Physical functioning
92 ± 10.4
91 ± 9.5
0.69
Emotional functioning
83 ± 18.2
79 ± 18.7
0.53
Social functioning
90 ± 12.2
91 ± 9.0
0.77
School functioning
77 ± 18.9
72 ± 17.8
0.40
Psychosocial functioning
83 ± 12.9
81 ± 11.3
0.51
QOL ≥ 18 years (SF-36; mean ± SD)
N = 26
N = 47
Physical functioning
95 ± 12.1
96 ± 15.9
0.71
Social functioning
91 ± 21.4
92 ± 13.4
0.92
Role limitations, physical
96 ± 15.3
95 ± 19.5
0.74
Role limitations, emotional
86 ± 28.6
94 ± 21.2
0.19
Mental health
80 ± 13.6
80 ± 11.8
0.91
Vitality
69 ± 16.6
75 ± 13.8
0.11
Pain
91 ± 17.6
93 ± 14.4
0.74
General health
76 ± 18.6
80 ± 15.6
0.37
Health change
53 ± 19.1
54 ± 14.7
0.84
QOL = quality of life. Scores range from 0 to 100. Higher scores indicate better QOL.
Urinary tract symptoms and disease-specific QOL outcomes were not different between adults and adolescents nor between gender. Urinary tract symptoms were reported by 42% of adults and 33% of adolescents, p = 0.33. Subsequent disease-specific QOL scores were 96 ± 5.4 in adults versus 95 ± 12 in adolescents, p = 0.61. Males expressed urinary tract symptoms in 34% versus 37% of females, p = 0.76. Subsequent disease-specific QOL scores were respectively, 99 ± 2.2 and 96 ± 8.0, p = 0.09.
Urological characteristics of former patients
The mean age at first presentation in childhood was 7.8 ± 2.2 years. Most patients were diagnosed with OAB with or without UI (N = 27; 53%) or dysfunctional voiding with or without UTIs (N = 24; 46%). The mean treatment duration was 3.8 ± 2.3 years.
A complete response (100% dry, no remaining complaints) was achieved in 24 patients (46%), whereas partial and no response (50–99% and <50% decrease in symptoms or UI, respectively) were observed in 14 patients each (27%) [
The standardization of terminology of lower urinary tract function in children and adolescents: update report from the standardization committee of the International Children’s Continence Society.
]. The mean elapsed time between discharge at childhood and the present study was 8.8 ± 4.4 years. ADHD reported at the time of treatment in childhood was reported in 3/52 children.
Treatment outcome of former patients related to current urinary tract symptoms
There were no differences in storage symptoms, voiding symptoms and UI subdivided by childhood treatment outcome (data not shown).
Median and range of storage symptoms (OAB-q symptom bother score) were 19 (8–21), 11 (5–21) and 13 (3–21) for former patients with complete, partial or no response, respectively p = 0.41. Furthermore, 42% (N = 10), 21% (N = 3) and 21% (N = 3) of former patients with complete, partial and no response had a current symptom bother score >22, indicating significant storage symptoms, p = 0.23.
Both voiding symptoms as UI were equally expressed by former patients with complete, partial or no response of their treatment in the past, respectively p = 0.17 and p=0.58 (data not shown).
Former patients and predictability of urinary tract symptoms later in life
A longer treatment duration of former patients in childhood was the only independent risk factor for urinary tract symptoms in adolescence and young adulthood (OR 1.5, 95% CI 1.1–2.0) in this study, Table 4. Median and range OAB-q symptom bother scores for those with treatment durations below and above 2.5 years were 10 (5–15) and 20 (8–25; p = 0.04), respectively.
Table 4Logistic model of prognostic factors for urinary tract symptoms later in life after treatment in childhood.
Odds ratio
95% CI
p-value
Treatment duration in years
1.5
1.1–2.0
0.01
Treatment response
Complete response
Reference
No response
6.5
1.0–41
0.05
Partial response
1.8
0.2–15
0.57
(Constant)
(0.03)
(0.05)
CI: Confidence interval. Variable without a significant predictive value and not shown in the table: age at the end of treatment <12 or ≥12 years (p = 0.45).
Our results revealed more urinary tract symptoms, lower disease-specific QOL scores and equal general QOL scores and mental health scores in former patients versus healthy age-matched controls. A longer treatment duration at childhood was predictive for subsequent urinary tract symptoms later in life.
Several authors have studied the association of childhood LUTD and urinary symptoms in adulthood compared to healthy controls [
]. The present study findings support this association since almost 60% of former patients experienced urinary tract symptoms, compared to 19% of the healthy age-matched controls.
In our study, urge UI, intermittency, feeling of incomplete emptying, nocturia and SUI were all more often reported by former patients. Costantini et al. found more UI, intermittency and straining reported in young women with a history of childhood LUTD (N = 120) versus healthy controls (N = 134) [
]. Small differences in exact percentages and types of symptoms among different studies and our results can be explained by definition, expression and interpretation among questionnaires and subjects.
To our knowledge, this is one of the few studies that includes adolescents and subjects of both gender since most studies include young adult women. No differences were observed between different age groups (adolescents versus adults) and genders (female versus male) in number of urinary tract symptoms and subsequent disease-specific QOL in our study. However, results have to be interpreted with caution since our subgroups are small.
In our study, treatment response in childhood was not a decisive factor for urinary tract symptoms later in life. Urinary incontinence was reported by 43% (N = 22) of all former patients and as common in those with a complete response of treatment in childhood as those with no response. Other percentages are seen in other studies. Vijverberg et al. found a good outcome in 84% in their former patients, whereas 16% had a moderate or poor outcome, including one accident per week [
]. However, their outcome measurements were differently defined compared to ours as ICCS standards changed over time.
Our findings imply either a less sustainable effect of childhood treatment or de novo development of other types of UI or both. Relapse of urge UI and de novo SUI in our former patients were seen in 21% and 31%, respectively despite a complete treatment response in childhood. Thus, both relapse and de novo complaints contributed to the higher percentages in our study, but because outcome measurements and definition of treatment success are different and changed over time, it remains difficult to compare different studies.
The present study revealed that even those who received successful treatment in childhood have high odds of having not only UI but also other type of urinary tract symptoms later in life. A complex interplay of heritability, environmental factors and alterations in cerebral neurological networks over time may explain an individual's predisposition to developing LUTD [
]. Successful treatment in childhood does not seem to completely alter this predisposition. Prospective studies with larger numbers are needed to confirm our findings, especially as the number of former patients (N=52) is underpowered leading to a potential risk for Type II error.
Remarkably, 10% (N = 7) of the controls and 27% (N = 14) of the former patients in this study reported SUI, which is relatively high for the specific age group. Other studies have also reported this hidden prevalence of urinary tract symptoms with 16–26% of SUI in healthy nulligravid young women [
]. Since some symptoms might not be extensive enough or bothersome enough to seek medical attention, percentages are probably higher than initially expected for the general population.
Disease-specific quality of life
Clinical relevance of significantly different disease-specific QOL scores in our former patient groups versus healthy controls remain questionable as overall and subdomain scores were still 93 or above, indicating only a minimal effect of urinary tract symptoms on disease-specific QOL.
Coyne et al. found worse disease-specific QOL in individuals with severe urinary tract symptoms than in individuals with minimal or no urinary tract symptoms. In addition, those with complaints in all subdomains (voiding, storage and postmicturition) scored worse than subjects with complaints in only one domain [
]. In our study, most subjects experienced complaints in only one domain and reported little impaired disease-specific QOL, which is line with Coyne et al.’s results.
General QOL and psychosocial outcome/mental health
This study found equal outcomes in general QOL and psychosocial wellbeing/mental health for former patients and healthy controls. As mentioned previously disease-specific QOL scores were lower- but probably without significant clinical relevance-in former patents.
Several authors have studied the relationship between mental health, disease-specific QOL and urinary tract symptoms [
]. Another study found that urge UI in women was a significant independent risk factor for anxiety (odds ratio [OR] = 1.4; 95% confidence intervals [CI] = 1.2–1.6) and depression (OR = 1.4; 95% CI = 1.2–1.7)23. New cases of urge UI were associated with anxiety at baseline but not with depression. On the one hand, psychological conditions and anxiety or depression are associated with LUTD. On the other hand, LUTD itself may affect general QOL, disease-specific QOL and mental health/psychosocial wellbeing in both childhood and adulthood [
]. It remains difficult to determine what comes first, chicken or egg.
Predictive factor of former patients for urinary tract symptoms later in life
Childhood treatment duration >2.5 years was found to be associated with more subsequent urinary tract symptoms later in life. Treatment outcome was not predictive, but subgroups are likely too small to detect any difference.
Other studies have also identified psychological comorbidity as a predictive factor [
]. Noticeably, psychiatric conditions-especially ADHD and autism-were significantly more reported in our former patients (35%) versus controls (10%). However in our study, these numbers reflect presence of psychological conditions at the time of the study and not at the time of childhood treatment. Therefore we were unable to include them in our predictive model. Reported psychological comorbidity at the time of childhood treatment revealed only three cases. Underestimation of this number is likely as attention for psychological comorbidity increased throughout the last decade.
The present study was limited as the number of former patients was underpowered. In addition a selection of patients returned the survey. Over time, different types of patient files were used (i.e., paper and electronic), and incomplete data transfer from one system to the other has likely induced an information bias, making the retrospective chart analysis difficult. Furthermore, valid contact data were missing since former patients had moved. Different instruments were used to evaluate general QOL among age groups (PedsQOL <18 years and SF-36 ≥ 18 years). Subgroups are too small to detect reliable differences. Former patients and controls significantly differed in demographics and psychological comorbidity, which might have a substantial effect on certain outcomes.
Conclusion
Adolescents and young adults treated for childhood LUTD are more likely to have urinary tract symptoms later in life; however, general QOL and psychosocial wellbeing seem not significantly impaired. Physicians should be aware of these results and consult their patients accordingly.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
The standardization of terminology of lower urinary tract function in children and adolescents: update report from the standardization committee of the International Children’s Continence Society.
Definitions, indications and practice of urotherapy in children and adolescents: - a standardization document of the International Children’s Continence Society (ICCS).
Urotherapy in children: quantitative measurements of daytime urinary incontinence before and after treatment according to the new definitions of the International Children’s Continence Society.
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