Bowel Function, Urinary Tract Function, and Health-related Quality of Life in Males With Anorectal Malformations

Bowel Function, Urinary Tract Function, and Health-related Quality of Life in Males With Anorectal Malformations | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Bowel Function, Urinary Tract Function, and Health-related Quality of Life in Males With Anorectal Malformations Joshua Gertler, Anna Löf Granström, Jenny Oddsberg, Anna Gunnarsdóttir, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4595839/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jun, 2024 Read the published version in Pediatric Surgery International → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose There is a knowledge gap regarding long-term outcomes for males undergoing surgery for an anorectal malformation (ARM). The purpose of this study was to investigate bowel function, bladder function and health-related quality of life (HRQoL) in male patients with an anorectal malformation. Methods This cross-sectional questionnaire-based study included males treated for ARM at our institution between 1994 and 2017. Bowel function was assessed with bowel function score (BFS) whilst urinary tract function was assessed with Lower Urinary Tract Symptoms (LUTS) questionnaires. Health-related quality of life (HRQoL) was investigated using age-relevant questionnaires (KIDSCREEN and PGWBI). Patient characteristics were retrospectively collected from the medical records and descriptive statistics were used for analysis. Functional outcomes were compared with gender and age-matched controls whilst HRQoL was compared to normative data. The study was approved by ethics review authorities. Results A total of 58 (44.6%) of 130 males responded to the questionnaires. Regarding bowel function, twenty-four (42.1%) of 57 patients and 81 (95.3%) of 85 controls, respectively, reported a well-preserved bowel function represented by a BFS ≥ 17 (p < 0.001). Soiling issues and ‘feels urge’ items improved significantly with age. In a linear regression model, BFS increased significantly with age. For most parameters, the proportion of ARM patients with lower urinary tract symptoms was larger, though not significantly, compared to the controls. However, straining and stress incontinence were reported significantly more often by ARM patients. In patients and controls, voiding outcomes in terms of prevalence of having symptoms and the number of cumulative symptoms drop with increasing age. Children and adults reported similar or, in some domains, better HRQoL outcomes when compared to normative European data. Conclusion Bowel function is impaired in male patients with ARM but significantly improves with age. Urinary tract function was affected, but overall comparable to the controls. HRQoL was unaffected. No significant association between the studied outcomes could be shown. anorectal malformation adulthood bowel function urinary tract function QoL surgery Figures Figure 1 Figure 2 Figure 3 Figure 4 Highlights -What is currently known about this topic? Functional and health-related quality of life outcomes into adulthood for males with anorectal malformation (ARM) are still scantily studied. -What new information is contained in this article? HRQoL in male patients is unaffected in our cohort and the negatively impacted bowel function alleviates with increasing age. Also, lower urinary tract function improves with age. Introduction Congenital anorectal malformations (ARM) are one of many congenital anomalies amongst newborns. The birth prevalence of ARM in Sweden is approximately 1:3000 [1, 2]. There is a small predominance of male infants born with ARM with a sex ratio of 1.3:1 [1]. Associated malformations occurred in 50–67% patients with ARM in a registry-based study of 17 European regions [3]. It is assumed that associated malformations have a negative impact on overall outcomes of patients with ARM. Classification of ARM subtypes is essential to correctly treat patients and to facilitate comparative research in national and international settings. Previously, the Wingspread and Peña classifications were widely used. More recently, the clinically orientated Krickenbeck classification has been adopted[4–6]. Male anomalies include perineal cutaneous fistula, bulbar rectourethral and prostatic rectourethral, recto bladder-neck vesical fistula, atresias without a fistula as well as anal stenosis. The vast majority of ARM patients require corrective surgery in the neonatal period or infancy. Peña and DeVries introduced the existing surgical techniques, a posterior sagittal anorectoplasty (PSARP), in the early 1980’s[7]. Minimally invasive techniques using laparoscopic-assisted anorectoplasty (LAARP) now has a place in the management of selected male ARM patients [8]. The survival rates in infants with ARMs have steadily increased over the years alluding to the progress of surgical and neonatal care. As a result, a shift in treatment goals has occurred from survival to optimizing functional outcomes and preserving a good health-related quality of life (HRQoL). Composite and controlled data for outcomes of bowel function, urinary tract function and quality of life are lacking. Amongst published work, quality of life and bowel function is shown to be impaired in patients with ARM [9–11] Our group recently investigated these outcomes in female patients[12]. Here, we focus on male patients and aim to assess their outcomes into adulthood in a controlled study-design. Methods Study Design This was cross-sectional questionnaire-based study. The study was registered in ClinicalTrials.gov (NCT04901819). Study setting Individuals with ARM managed at the Unit of Pediatric Surgery at Karolinska University Hospital, Stockholm, Sweden. In 2024, Sweden has a population of roughly 10.6 million persons. Participants All surgically managed males with ARM at our institution between 1994 and 2017 were eligible for the study. A database of identified eligible patients was created. The ARM subtypes which were included were perineal fistulas, rectourethral fistulas (both bulbar and prostatic), recto bladder-neck fistulas as well as atresias without fistulas. Deceased patients and patients without surgical interventions were excluded from the study. In extension, patients with Currarino syndrome, Down’s syndrome and patients with major intellectual disabilities were excluded from the study. After informed consent, participants and, or caregivers were asked to answer a composite questionnaire pertaining to the focus of study. Participants had the option to respond using paper mail or a digital platform (REDCap). A reminder was mailed to non-respondents after 4 and 8 weeks, respectively. Age categories (4–7, 8–12, 13–17, 18–26 years) determined which questionnaires were received. A control group of 2518 healthy age-matched individuals were randomly selected by Statistics Sweden from the Sweden Population Registry and invited to respond to Bowel function score (BFS) and Lower Urinary Tract Symptoms (LUTS) questionnaires. One hundred-ninety-nine (8%) controls responded and 88 of them (44%) were males and thus used for comparison. Normative data were used to compare HRQoL outcomes[13]. Data sources and variables Patient characteristics Patient characteristics and clinical details were recorded retrospectively from the medical records. These data included information about associated anomalies, ARM subtype according to Krickenbeck Classification, surgical procedures and age at time of the study. The follow-up date was set to the 15th of June 2021. Bowel Function Bowel function was assessed in all age categories using the previously validated BFS developed in the Finnish population [14, 15]. A BFS score of ≥ 17 of maximum 20 was used as an indicator of well-preserved bowel function as described previously by Kyrklund et al. [14]. Bowel function was evaluated in patients regardless of the use of laxatives, enemas, or antidiarrheal medication. No patients included in the cohort had enterostomies. Urinary Tract Function Urinary tract function was examined in all age categories with the validated 9-question Lower Urinary Tract Symptoms (LUTS) questionnaire [16]. Three out of seven items in the employed LUTS questionnaire were based on an adaptation from the previously validated Danish Prostatic Symptom Score [17]. Patients with urinary diversion or who performed clean intermittent catheterization (CIC) were excluded prior to data analysis. Urinary tract function outcomes will be presented descriptively, the major endpoint being the prevalence of urinary incontinence defined as involuntary urinary leakage. Health-Related Quality of Life (HRQoL) To assess children’s and adolescents’ (8 to 17 years old) subjective health and well-being, the KIDSCREEN-52 questionnaire was used as a validated instrument [18, 19]. The instrument covers 10 HRQoL dimensions encompassing Physical Well-being, Psychological Well-being, Moods & Emotions, Self-Perception, Autonomy, Parent Relation & Home Life, Financial Resources, Social Support & Peers, School Environment and Social Acceptance (Bullying). The generic questionnaire is designed for both healthy and chronically ill children, also providing European normative data for comparison in this study [18]. In adults (18 to 26 years old), the validated instrument Psychological General Well-Being Index (PGWBI) was employed [13, 20, 21]. The instrument includes six dimensions comprising a total of 22 items with a maximal total score of 110, the higher the score the better HRQoL. The dimensions include Anxiety, Depressed Mood, Positive Well-being, Self-Control, General Health, and Vitality. Outcomes of the survey are interpreted as follows; 0–60 “Severe Distress”, 61–71 “Moderate Distress”, 72–92 “No Distress”, and 93–110 “Positive Well-being” [21]. A score of roughly 80 is considered a mean score in large reference groups [22, 23]. Normative data for male healthy individuals were used when analyzing PGWBI outcomes. Statistical Methods Categorical variables were presented using frequencies and proportions whereas continuous variables were presented as median with interquartile range (IQR) or mean with standard deviation (SD). LUTS and BFS values were compared between patients and age-matched female controls using the Fisher's exact and Wilcoxon Sum Rank Tests, respectively. Trends between age groups and BFS item scores in the patient group were analyzed using Asymptotic Linear-by-Linear Association Test. The overall BFS sum-score was compared between age groups within cases and controls separately using non-parametric test (Jonckheere-Terpstra Test). For LUTS, a logistic regression model comparing patients and controls and adjusting for age as a continuous variable was designed to estimate the Odds (OR) for having any LUTS (defined as presence of at least one symptom). KIDSCREEN values were translated to T values using the KIDSCREEN instruction manual and compared to European normative data for children & adolescents aged 8–17 years old using a t-test [10]. Likewise observed PGWBI scores were compared to reference scores using a t-test [13]. The Spearman correlation test was used to analyze the association between BFS and the HRQoL variables (rho > 0.7 = strong correlation, > 0.4 moderate association, 0.2–0.4 = no correlation). T-tests were used to analyze relationships between the presence of LUTS and HRQoL variables. A significance level of p < 0.05 was used. Ethical considerations The study was approved by the Swedish Ethical Review Authorities. Results Patient Characteristics The inclusion process is summarized in Fig. 1 . The median age of the included patients and controls at the time of the study was 11 (IQR 7.8) years and 11.5 (IQR 8) years, respectively. One patient had Down syndrome and was thereby excluded from the study. Forty-six responders were 4–17 years of age and 11 were 18–26 years of age. The number of individuals included in each age group and their median ages are summarized in Supplementary Table 1. Thirty-four (59.6%) patients received a stoma neonatally. A PSARP was performed in 26/57 (45.6%) patients whilst a limited PSARP was employed in 25/57 (43.9%). One child and 5 adult patients had missing data concerning type of primary surgery. Forty percent of the patients had been treated for a perineal fistula and a just over a quarter (25.9%) had had a rectourethral fistula (Table 1 ). Due to lack of specificity in reporting in medical records, the rectobulbar and rectoprostatic urethral fistulas were pooled into one subgroup depicted as rectourethral fistulas. Associated malformations, for those included in the study, were common with 48.3% of patients having one or more associated malformation. VACTERL association was found in 15.5% of patients. Nine patients currently employed anterior continence enemas (ACE). Table 1 Patient Characteristics of the 58 responders. (Abbreviations: Interquartile range, IQR; anorectal malformation, ARM; antegrade continence enema, ACE; VACTERL, vertebral-anal-cardiac-tracheo-esophageal-renal-limb) N (% Missing Data (n) Median age at follow-up (Years, Median, IQR) 11 (7.75) 0 Type of ARM 7 Perineal Fistula Rectourethral Fistula Atresia without Fistula Recto Bladder-neck Other (e.g. stenosis) 23 (39.7) 15 (25.9) 7 (12.1) 3 (5.1) 3 (5.1) Associated malformations Esophageal atresia Cardiac malformation Urinary tract anomalies Vertebral anomalies Tracheal anomalies Limb abnormalities VACTERL association Spinal cord abnormality 28 (48.3) 4 (6.9) 9 (15.5) 12 (20.7) 12 (20.7) 0 2 (3.4) 9 (15.5) 11 (19.0) 5 11 Permanent stoma at follow-up 0 Antegrade Continence Enema (ACE) 8 (13.8) Permanent Urinary Diversion 2 (3.4) Current Occupation among patients ≥ 18 years, n = 12 Student Full-time employed Part-time employed On sick-leave 6 (50.0) 3 (25.0) 4 (33.3) 0 Use of laxatives or enemas excluding ACE Children and Adolescents Adults 25 (54.3) 5 (41.7) Bowel Function Score No patients had a permanent enterostomy at the time of the study. Patients with ACE were included in the analysis. The median BFS for patients was 16 (IQR 5) compared to 19 (IQR 1) for controls (Fig. 2 A) (p < 0.001). Due to missing values in the control responses 85/88 controls could be used for data analysis. Differences in Median BFS scores between age groups within the cohort were statistically significant (Fig. 2 B and 3 ). Both a non-parametric test (Jonckheere-Terpstra Test) and a linear regression model showed statistically significant increases in BFS with age, with p-values of 0.034 and 0.008, respectively. For every additional year of age, BFS is shown to increase 0.22 arbitrary units. A well-preserved bowel function defined as BFS ≥ 17 of 20 was found in 42.1% (24/57) of patients compared to 95.3% (81/85) in controls (p < 0.001) (Fischer’s exact test). In the patient cohort, 37.0% (17/46) of children and adolescents and 63.6% (7/11) of adults reported a well-preserved bowel function. The patients reported statistically significant lower scores across all items in the questionnaire when compared to the control group, except for their defecation frequency, displayed in Table 2 . Table 2 Bowel Function Scores per item and age groups, comparing cohort and controls. * Fishers Exact Test. (Abbreviations: Interquartile range, IQR; Bowel Function Score, BFS) Item Score Cohort, n (%) Controls, n (%) p-value* n 57 88 Age, mean (SD) 12.33 (6.13) 12.15 (5.28) 0.846 Age group 4–7 years 8–12 years 13–17 years 18–26 years 13 (22.8) 19 (21.6) 0.957 21 (36.8) 32 (36.4) 12 (21.1) 22 (25.0) 11 (19.3) 15 (17.0) Feels/reports the urge to defecate 0 2 ( 3.5) 1 ( 1.1) < 0.001 1 10 (17.5) 1 ( 1.1) 2 11 (19.3) 5 ( 5.7) 3 34 (59.6) 81 (92.0) Ability to hold back defecation 0 6 (10.5) 1 ( 1.1) < 0.001 1 8 (14.0) 1 ( 1.1) 2 15 (26.3) 3 ( 3.4) 3 28 (49.1) 83 (94.3) Frequency of defecation 1 13 (22.8) 12 (13.8) 0.182 2 44 (77.2) 75 (86.2) Soiling 0 4 ( 7.0) 0 ( 0.0) < 0.001 1 11 (19.3) 2 ( 2.3) 2 22 (38.6) 21 (24.1) 3 20 (35.1) 64 (73.6) Accidents 0 1 ( 1.8) 0 ( 0.0) < 0.001 1 4 ( 7.0) 0 ( 0.0) 2 11 (19.3) 4 ( 4.5) 3 41 (71.9) 84 (95.5) Constipation 0 10 (17.5) 1 ( 1.1) < 0.001 1 16 (28.1) 2 ( 2.3) 2 10 (17.5) 11 (12.6) 3 21 (36.8) 73 (83.9) Social problems 0 2 ( 3.5) 0 ( 0.0) < 0.001 1 7 (12.3) 1 ( 1.1) 2 8 (14.0) 1 ( 1.1) 3 40 (70.2) 86 (97.7) BFS score (median [IQR]) 16.00 [13.00, 18.00] 19.00 [19.00, 20.00] < 0.001 BFS ≥ 17/20, n (%) 0–16 33 (57.9) 4 ( 4.7) < 0.001 17–20 24 (42.1) 81 (95.3) A linear-by-linear asymptotic association test was used and suggested statistically significant trends in 2 of the 7 BFS-items. A positive trend was seen in the ‘feels urge’ item where it improved with increasing age group (p = 0.026). Further, a positive trend was seen in ‘soiling’ where this issue mitigated with increasing age group (p = 0.001). No other significant trends were identified relating to individual BFS-items and age. Urinary Tract Function One child and one adult, both having sacral dysgenesis, used CIC and were excluded from this analysis. The sense of urgency and the need to strain were the most common symptoms in the cohort with 17.2% and 16.3%, respectively, having these symptoms to some degree. For the controls, bedwetting was the most common symptom reported with a percentage of 11.3. Fishers Exact Test was performed to compare age group distribution and overall LUTS prevalence between patient and controls, no statistical differences (p = 0.975 and p = 0.299, respectively) were observed. However, the estimated Odds Ratio for having LUTS (LUTS > 0) as a patient was 1.8 times higher than for controls (95% CI 0.85, 3.83). Stress incontinence and straining during urination were significantly higher in the cohort (p = 0.031 and 0.007, respectively). Bedwetting in the cohort was reported marginally more frequently, p = 0.050. Including spontaneous leakage, as a measure of voiding incontinence, no other factors were significantly different between patients and controls. No adult patients in the cohort reported stress incontinence, urge incontinence, bedwetting, social problems due to incontinence or spontaneous leakage. In patients and controls, both the prevalence of having symptoms and the number of cumulative symptoms drop with increasing age. A logistic regression model using age as a continuous variable showed that the odds (OR) decreases for LUTS 0.87 times (95% CI 0.80, 0.93) for every additional year of age (p < 0.001). HRQoL KIDSCREEN for children and adolescents Visually, the normalized mean domain T-values in the cohort did not differ significantly from the age- and gender-matched European normative data (Fig. 4 ). Paradoxically, cohort patients had a significantly higher score in the Financial Resources, Parent Relations, School Environment and Bullying social acceptance domains (p = 0.000, 0.026, 0.002, 0.001, respectively). PGWBI for adults The mean normalized PGWBI for the cohort was 81.3 compared to the reference data having a mean score of 73.9 (p = 0.002). Table 3 summarizes the cohort and normative data per domain. The cohort scored significantly higher in several domains including ‘Anxiety’ and ‘General Health’. The cohort did not score inferiorly to the norm data in any domain, graphically visualized in Fig. 4 . Table 3 PGWBI domain scores compared to norm data. (Abbreviation: Psychological General Well-Being Index, PGWBI) PGWBI Domain Cohort, Mean (SD) Normative Data, Mean (SD) p-value Anxiety 80.0 (9.6) 71.4 (19.3) 0.020 Depressed mood 88.7 (7.7) 84.2 (16.7) 0.101 General Health 89.3 (8.4) 77.2 (19.2) 0.001 Positive Well-being 72.5(12.7) 64.1 (18.9) 0.067 Self Control 88.7(9.5) 82.5 (17.6) 0.069 Vitality 74.5(10.1) 68.3 (18.9) 0.085 Index Score 81.3 (5.2) 73.9 (15.5) 0.002 One patient scored within the “severe distress” bracket (0–60 points). This patient also utilized CIC and had the poorest BFS (13/20) of the adult group. Eight patients (72.7%) had “no distress” (72–92) and two patients (18.2%) reported “being positive” (72–110). None of the adult patients were on sick leave at follow-up time and 90.9% of them did not subjectively feel that their choice of occupation was affected by their ARM (Table 1 ). Composite Outcomes KIDSCREEN and BFS A Spearman correlation test (Rho = ρ) was performed to evaluate correlation between KIDSCREEN item T-scores and BFS. Overall, no correlations could be found except for the patient’s autonomy (ρ = 0.525, > 0.4 = moderate correlation) and financial aspects (ρ = 0.442). There is therein a moderate association between a higher BFS and better subjective autonomy and their perceived financial situation. KIDSCREEN and LUTS Assuming that KIDSCREEN T-values have a normal distribution, a T-test was used to see if a relation was present between KIDSCREEN items and the presence of LUTS (excluding history of UTI). No associations were found. PGWBI, LUTS and BFS The relationships of PGWBI contra LUTS and BFS were analyzed, however, no associations could be shown. ARM-subtype and BFS The subtype groups for perineal (n = 21) and rectourethral (n = 14) fistulas in children and adolescents were large enough to analyze where 62% and 14% had a BFS ≥ 17/20, respectively (Exact test p = 0.007). Discussion Key Findings The bowel function of males treated for ARM was grossly impaired across all age groups when compared to healthy controls. For the cohort, 42.1% reported an acceptable bowel function compared to 95.3% in the controls. Bowel function in the cohort improved with 0.22 units per year of age and 63.6% of adult patients reported a BFS of ≥ 17/20. Soiling issues and the ability to feel the urge to defecate improved significantly in the cohort with increasing age group. Contrarily to findings by Rintala et al and our previous study on females, constipation issues did not change with increasing age [12, 24]. Voiding outcomes in general were comparable to the controls. Nonetheless, LUTS were more common in the ARM group compared to the controls. The OR decreases for LUTS 0.87 times for every additional year of age. The sense of urgency and the need to strain to urinate were the most common LUTS in the cohort. Involuntary leakage did not occur in any of the adult patients in the study. In accordance with a recent systematic review showing a high LUTS prevalence (36%) 10-years after surgical repair, 41.8% of patients in our cohort had at least one LUTS [25]. Our data is in the middle range of what has been reported in the literature (18–72%) [25, 26]. The recent review article describes a UTI rate of 36.4% compared to 13% in our cohort [26]. In accordance with previous results, HRQoL was preserved with children and adolescents in this cohort [12, 27]. Surprisingly, the cohort scored significantly higher in the domains of Financial Resources, Parent Relations, School Environment and Bullying social acceptance. Further, an association was found between BFS and the children’s feelings of autonomy and their financial perceptions. Regarding autonomy, this relation was recently described even for female ARM patients in our previous study [12]. Hypothetically, an acceptable bowel function could influence autonomy, not having to ask for help or assistance if, for example, fecal accidents happen. In the adult group, the HRQoL was preserved and paradoxically scored higher on the overall score when compared to normative data. Nearly three-quarters of patients reported “no distress” which is the same category where the mean result (80) is found in large reference groups [23]. The PGWBI scores could not be associated statistically to either LUTS or BFS. Interpretation Through literature review, few studies have focused on gender-specific outcomes after surgical repair of ARM while comparing them to matched controls. In extension to our previous research, “partially pertaining to anatomical differences, the phenotypes of the malformations differ between males and females and thus should be studied separately”[12]. Studying the genders separately has suggested major differences in the two groups. In males, BFS and LUTS improved with increasing age and even adult patients had a preserved HRQoL. This was not the case for our female cohort [12]. Choosing a suitable questionnaire was crucial for this study. The multivariate BFS by Rintala et al was employed to facilitate comparison of outcomes between present and future ARM studies [15]. Through literature review, BFS has been trending in recent years. Further, geographically neighboring Nordic countries, having similar sociocultural-economic structures and health care systems are deemed to be comparable on the population general health level [14]. This study confirms previously published results reporting bowel function impairment in ARM patients [28]. In this study 42.1% of patients had acceptable bowel function, a figure substantially higher than what we previously reported for females (32.6%) from the same center and time period [12]. This points to the heterogeneity of the malformation and gender-specific differences. A mean BFS of 15.1 (SD 4.0) in our study is comparable to 13.9 found by Kaselas et al, although Kaselas pooled females and males together. ARM subtype is of interest in relation to BFS, however, our cohort was too small to yield substantial power for most subgroup analyses. However, we found that perineal fistulas in children had better bowel function outcomes compared to children with recto-urethral fistulas. In 2005, Levitt and Peña concluded that constipation was the most common complication in patients who had undergone PSARP [29]. Second to soiling issues reported in 64.9% of our cohort, 63.2% of patients had some degree of constipation. Interpreting HRQoL of patients with congenital malformations is a challenge. For example, these patients were born with their condition and thereby their reference of HRQoL could arguably differ from that of the reference population. In children and adolescents in this study, their reported HRQoL was not inferior to the normalized reference data. In fact, our cohort scored higher on several items. These findings are in par with results reported by Wigander et al from a Swedish cohort of children with low ARM where patients and controls had comparable HRQoL (HAQL tool) [30]. A recently published paper by Beattie et al found conflicting results to ours where they used the PedsQL tool showing significantly impaired quality of life in children[31]. Further, Beattie et al reported no differences in QoL between genders in children with ARM. HRQoL studies performed by Hartmann et al show a large variation in quality of life in patients treated for ARM[32]. Patients doing very poorly are an urge for concern and must be identified early on by clinicians to implement extra care[33]. Örtqvist et al recently reported in a multi-center Nordic study that even patients operated on for a cloacal malformation had similar HRQoL compared to healthy a Swedish Population [34]. Critical comparison of studies is made difficult due to study design differences as well as the use of different investigating tools. Few studies have focused on the span of ages into adulthood for males regarding HRQoL and there lies no consensus for which HRQoL tool should be used. For our purposes, the KIDSCREEN tool was suitable as it has been broadly used in the Nordic setting and has normative data on a large scale. In adult males from this cohort, their HRQoL was not either found be inferior to normative European data. Published work on this topic with similar cohorts is scanty. A thirty-year-old paper by Hassink et al looking at 58 adults having been operated for a high ARM observed that “most aspects of QoL and mental health did not differ from those of the general population” [35]. It could be speculated that coming into puberty and adulthood leading to sexual debut could lead to impaired HRQoL. However, this does not seem to be the case in our cohort. Composite outcomes in this setting have been scantily studied to this point. We aimed to analyze potential associations between HRQoL, bowel function and urinary tract function. Parallelly to the previously published female cohort, BFS is even shown to be associated to the feeling of autonomy in male children [12]. Further, male children and adolescents’ BFS correlates moderately to the financial resources item of HRQoL. These aspects are assumed to be influenced by several variables which is why the associations found were moderate. Children with perineal fistulas statistically had better bowel function outcomes than children with rectourethral fistulas. This is in par with previous research where higher, more complex malformations have been shown to have impaired bowel continence [31, 36, 37]. In general, the relatively small groups of patients and large number of variables make these analyses challenging. Furthermore, certain analyses which had been envisioned were unable to be carried out. For example, we collected data on spinal and other associated anomalies, however, the amount of missing data proved to be too large to yield generalizable results (data not published). Overall, the same applies for the influence that ARM-subtype might have on BFS, LUTS and HRQoL. Limitations To reduce confounding factors, the heterogenicity of the cohort was limited. Selection bias of the responders was minimal as potential participants met the inclusion criteria before asked to answer the questionnaires. Yet, it is possible that patients in need of medical attention have a greater inclination to participate which would create a selection bias. A first limitation was the sample size. Our intended secondary aim to examine long-term outcomes per ARM-subtype proved difficult to answer due to the low response rate (44.6%) subsequentially making subgroups too small to generate statistical power concerning certain issues. Additionally, the response rate in the control group was likewise low. A second limitation involves the presence of ongoing treatments with laxatives and, or antidiarrheal medications, which the healthy controls were not exposed to. A third and final limitation is the cross-sectional study design. Not having followed a specific patient over time, it is difficult to evaluate changes in outcomes over time. For instance, we cannot conclude that a specific ARM patients’ BFS improves with age, although there is a general difference between age groups. We can, however, indicate that even LUTS prevalence decreases with increasing age and that HRQoL is preserved in all ages. Another factor potentially influencing outcomes if the heterogenicity of ARM-subtype complexity per age group. As the number of individuals with a specific subtype varied per age group, this could represent a confounding factor when interpreting results. A causality relationship between HRQoL and the congenital malformation could not be shown in this study. HRQoL is multifactorial and the response-shift umbrella concept should always be considered when interpreting HRQoL data [38]. Conclusion Roughly 40% of the male ARM patients reported well-preserved bowel function, a function that improved with age. LUTS prevalence diminished with age and no adults had involuntary urinary leakage, however, it must be noted that patients using CIC were excluded. Neither children nor adults were found to have an inferior HRQoL when compared to norm European data. Composite variable analysis proved difficult. These findings confirm the importance of transitioning male adolescents to adult care that can provide expertise in the sequelae of anorectal malformations. Abbreviations ACE- Antegrade Continence Enema ARM- Anorectal Malformation BFS- Bowel Function Score CI- Confidence Interval CIC- Clean Intermittent Catheterization HRQoL- Health-Related Quality of Life IQR- Interquartile Range PGWBI- Psychological General Well-Being Index PSARP- Posterior Sagittal Ano-Recto-Plasty LAARP- Laparoscopically Assisted Ano-Recto-Plasty LUTS- Lower Urinary Tract Symptoms SD- Standard Deviation UTI- Urinary Tract Infection VACTERL- vertebral-anal-cardiac-tracheo-esophageal-renal-limb Declarations Financial Support Statement: The study has been supported by grants from Kronprinsessan Lovisa’s Förening för Barnasjukvård, Sällskapet Barnavård, Barnforskningen from the Astrid Lindgren Children’s Hospital, and Birgitta and Carl-Axel Rydbeck Research Grant for Pediatric Research. Author Contribution Form (*) Type the name of each author next to the appropriate following categories: Study conception and design: JG, LÖ, TW Data acquisition: JG, LÖ, ALG Analysis and data interpretation: JG, LÖ, TW Drafting of the manuscript: JG, LÖ, TW Critical revision: LÖ, TW, ALG, JO, AG, AS Submit this form with the manuscript. Funding The study has been made possible by grants from Kronprinsessan Lovisa’s Förening för Barnasjukvård, Sällskapet Barnavård, Barnforskningen from the Astrid Lindgren Children’s Hospital and Birgitta and Carl-Axel Rydbeck Research Grant for Pediatric Research. Acknowledgements The authors thank Eva Hagel for her valued statistical support and our patients for their participation. We also thank Gustav Stenkvist for his help with initial data collection. Declarations of interest None Declaration of generative AI and AI-assisted technologies in the writing process Artificial Intelligence (AI) and AI-assisted technologies were not used in the preparation of this manuscript. (*): Modified from the authorship requirements of the J Am Coll Surg Disclosure: The authors have no actual or potential conflict of interest in relation to this manuscript. References Svenningsson A, Gunnarsdottir A, Wester T (2018) Maternal risk factors and perinatal characteristics of anorectal malformations. J Pediatr Surg 53(11):2183-8. Kancherla V, Sundar M, Tandaki L, Lux A, Bakker MK, Bergman JE, et al (2023) Prevalence and mortality among children with anorectal malformation: A multi-country analysis. Birth Defects Res 115(3):390-404. Wijers CH, van Rooij IA, Bakker MK, Marcelis CL, Addor MC, Barisic I, et al (2013) Anorectal malformations and pregnancy-related disorders: a registry-based case-control study in 17 European regions. BJOG 120(9):1066-74. Stephens FD SE (1986) Classification, identification and assessment of surgical treatment of anorectal anomalies. Pediatr Surg Int 1: 200-205. Pena A (1995) Anorectal malformations. Semin Pediatr Surg 4(1):35-47. Holschneider A, Hutson J, Pena A, Beket E, Chatterjee S, Coran A, et al (2005) Preliminary report on the International Conference for the Development of Standards for the Treatment of Anorectal Malformations. J Pediatr Surg 40(10):1521-6. deVries PA, Pena A (1982) Posterior sagittal anorectoplasty. J Pediatr Surg 17(5):638-43. Bischoff A, Pena A, Levitt MA (2013) Laparoscopic-assisted PSARP - the advantages of combining both techniques for the treatment of anorectal malformations with recto-bladderneck or high prostatic fistulas. J Pediatr Surg 48(2):367-71. Nah SA, Ong CCP, Saffari SE, Ong LY, Yap TL, Low Y, et al (2018) Anorectal malformation & Hirschsprung's disease: A cross-sectional comparison of quality of life and bowel function to healthy controls. J Pediatr Surg 53(8):1550-4. Svetanoff WJ, Kapalu CL, Lopez JJ, Fraser JA, Briggs KB, Rentea RM (2022) Psychosocial factors affecting quality of life in patients with anorectal malformation and Hirschsprung disease-a qualitative systematic review. J Pediatr Surg 57(3):387-93. Kyrklund K, Pakarinen MP, Taskinen S, Rintala RJ (2015) Bowel function and lower urinary tract symptoms in females with anterior anus treated conservatively: Controlled outcomes into adulthood. J Pediatr Surg 50(7):1168-73. Gertler J, Lof Granstrom A, Oddsberg J, Gunnarsdottir A, Svenningsson A, Wester T, et al (2024) Functional and Health-Related Quality of Life Outcomes into Adulthood for Females Surgically Treated for Anorectal Malformation. J Pediatr Surg Feb 20:S0022-3468(24)00093-9. doi: 10.1016/j.jpedsurg.2024.02.011. Epub ahead of print. PMID: 38443293. Olivier Chassany Es DD, Albert Wu (2004) The Psychological General Well-Being Index (PGWBI). User Manual. Kyrklund K, Koivusalo A, Rintala RJ, Pakarinen MP (2012) Evaluation of bowel function and fecal continence in 594 Finnish individuals aged 4 to 26 years. Dis Colon Rectum 55(6):671-6. Rintala RJ, Lindahl H (1995) Is normal bowel function possible after repair of intermediate and high anorectal malformations? J Pediatr Surg 30(3):491-4. Kyrklund K, Taskinen S, Rintala RJ, Pakarinen MP (2012) Lower urinary tract symptoms from childhood to adulthood: a population based study of 594 Finnish individuals 4 to 26 years old. J Urol 188(2):588-93. Schou J, Poulsen AL, Nordling J. The value of a new symptom score (DAN-PSS) in diagnosing uro-dynamic infravesical obstruction in BPH. Scand J Urol Nephrol 1993;27(4):489-92. Ravens-Sieberger U (2006) The KIDSCREEN questionnaires-Quality of life questionnaires for children and adolescents-Handbook. Pabst Science Publishers, Lengerich. 3rd edition 2016. Ravens-Sieberer U, Herdman M, Devine J, Otto C, Bullinger M, Rose M, et al (2014) The European KIDSCREEN approach to measure quality of life and well-being in children: development, current application, and future advances. Qual Life Res 23(3):791-803. Dupuy HJ. Edited by Wenger NK MM, Furberg CD, Elinson J (1984) The Psychological general Well-Being (PGWB) Index. In: Assessment of Quality of Life in clinical trials of cardiovascular therapies. Le Jacq Publishing. Chap 9. 170-83. Grossi E C, A (2014) Psychological General Well-Being Index (PGWB). Dimenas E, Carlsson G, Glise H, Israelsson B, Wiklund I (1996) Relevance of norm values as part of the documentation of quality of life instruments for use in upper gastrointestinal disease. Scand J Gastroenterol Suppl 221:8-13. Compare A (2016) Psychological General Well-Being Index (PGWB). Medical, Bracco, San Donato Milanese, Italy. Rintala RJ, Lindahl HG (2001) Fecal continence in patients having undergone posterior sagittal anorectoplasty procedure for a high anorectal malformation improves at adolescence, as constipation disappears. J Pediatr Surg 36(8):1218-21. Bjoersum-Meyer T, Kaalby L, Lund L, Christensen P, Jakobsen MS, Baatrup G, et al (2021) Long-term Functional Urinary and Sexual Outcomes in Patients with Anorectal Malformations-A Systematic Review. Eur Urol Open Sci 25:29-38. Reppucci ML, Harris KT, Wilcox DT, Peycelon M, Bischoff A (2023) Adult urological outcomes for patients with anorectal malformation. J Pediatr Urol. Ojmyr-Joelsson M, Nisell M, Frenckner B, Rydelius PA, Christensson K (2006) High and intermediate imperforate anus: psychosocial consequences among school-aged children. J Pediatr Surg 41(7):1272-8. Kaselas C, Philippopoulos A, Petropoulos A (2011) Evaluation of long-term functional outcomes after surgical treatment of anorectal malformations. Int J Colorectal Dis 26(3):351-6. Levitt MA, Pena A (2005) Outcomes from the correction of anorectal malformations. Curr Opin Pediatr 17(3):394-401. Wigander H, Nisell M, Frenckner B, Wester T, Brodin U, Ojmyr-Joelsson M (2019) Quality of life and functional outcome in Swedish children with low anorectal malformations: a follow-up study. Pediatr Surg Int 35(5):583-90. Beattie H, Subramanian T, Scudamore E, Middleton T, MacDonald C, Lindley R, et al (2024) Assessment of long-term quality of life, bowel and voiding function outcomes in patients with anorectal malformation at a single UK centre. Pediatr Surg Int 40(1):95. Hartman EE, Oort FJ, Aronson DC, Hanneman MJ, van Heurn E, de Langen ZJ, et al (2007) Explaining change in quality of life of children and adolescents with anorectal malformations or Hirschsprung disease. Pediatrics 119(2):e374-83. Hartman EE, Oort FJ, Sprangers MA, Hanneman MJ, van Heurn LW, de Langen ZJ, et al (2008) Factors affecting quality of life of children and adolescents with anorectal malformations or Hirschsprung disease. J Pediatr Gastroenterol Nutr 47(4):463-71. Ortqvist L, Holmdahl G, Borg H, Bjornland K, Lilja H, Stenstrom P, et al (2023) Bowel Control, Bladder Function, and Quality of Life in Children with Cloacal Malformations. J Pediatr Surg 58(10):1942-8. Hassink EA, Rieu PN, Brugman AT, Festen C (1994) Quality of life after operatively corrected high anorectal malformation: a long-term follow-up study of patients aged 18 years and older. J Pediatr Surg 29(6):773-6. Goyal A, Williams JM, Kenny SE, Lwin R, Baillie CT, Lamont GL, et al (2006) Functional outcome and quality of life in anorectal malformations. J Pediatr Surg 41(2):318-22. Levitt MA, Pena A (2007) Anorectal malformations. Orphanet J Rare Dis 2:33. Blome C, Augustin M (2015) Measuring change in quality of life: bias in prospective and retrospective evaluation. Value Health 18(1):110-5. Additional Declarations No competing interests reported. Supplementary Files Supplementarytable1.docx Supplementary table 1: Sample sizes of cohort and controls age groups. Cite Share Download PDF Status: Published Journal Publication published 27 Jun, 2024 Read the published version in Pediatric Surgery International → Version 1 posted Editorial decision: Accepted 18 Jun, 2024 Reviews received at journal 18 Jun, 2024 Reviewers agreed at journal 18 Jun, 2024 Reviewers invited by journal 18 Jun, 2024 Editor assigned by journal 18 Jun, 2024 Submission checks completed at journal 18 Jun, 2024 First submitted to journal 17 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4595839","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":315844967,"identity":"7b435d5e-3714-4d8f-bf15-7539f47c2494","order_by":0,"name":"Joshua Gertler","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYBACxgYGNjj7AAODjQEbHtXoWpgZgFrSCGsBAhQthw0Iqmdub3/2mKeGwa5f+vyBAx/3nDfmY2B/+ACvw3rOmBvzHGNIntmXzHBwxrPbZmwMPMZ4rWKckcMmzcPGkGxwhpnhMM+B2zZALWwS+LWkP5Pm+ceQbA/S8ufAOaAW9uc/8GtJMJPmbWOwM+ABamE4cADoMAYzfDpAfjGTnNsnkSBxhtngYM+BZGM2Zh5jvA4zBIaYxJtvNvb8PYwPH/w4YGc4v7394Qe8WhrAlERiA1yIGa+zGBjkobQ9AXWjYBSMglEwkgEAKiFDPsoP+mIAAAAASUVORK5CYII=","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":true,"prefix":"","firstName":"Joshua","middleName":"","lastName":"Gertler","suffix":""},{"id":315844968,"identity":"11ad69b2-d9ed-4950-9a97-4f00ed734401","order_by":1,"name":"Anna Löf Granström","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"Löf","lastName":"Granström","suffix":""},{"id":315844969,"identity":"1a8cb156-e78a-4121-a27d-3a9b68731499","order_by":2,"name":"Jenny Oddsberg","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Jenny","middleName":"","lastName":"Oddsberg","suffix":""},{"id":315844970,"identity":"db9d0828-15a5-483c-a257-89a94e999367","order_by":3,"name":"Anna Gunnarsdóttir","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Gunnarsdóttir","suffix":""},{"id":315844971,"identity":"ef0005ec-5fe7-4017-8f1a-36f9a2df3383","order_by":4,"name":"Anna Svenningsson","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Svenningsson","suffix":""},{"id":315844972,"identity":"fca92788-d390-4d4f-9126-cd0f6374ec4b","order_by":5,"name":"Tomas Wester","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Tomas","middleName":"","lastName":"Wester","suffix":""},{"id":315844973,"identity":"2b16cfd7-f40e-45eb-989b-9b40e30e984a","order_by":6,"name":"Lisa Örtqvist","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Lisa","middleName":"","lastName":"Örtqvist","suffix":""}],"badges":[],"createdAt":"2024-06-17 19:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4595839/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4595839/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00383-024-05746-5","type":"published","date":"2024-06-27T23:53:15+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60354385,"identity":"083e1308-2189-4ed0-a695-6c44dea92bab","added_by":"auto","created_at":"2024-07-15 23:52:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60732,"visible":true,"origin":"","legend":"\u003cp\u003eThe participant’s inclusion process\u003c/p\u003e","description":"","filename":"Figure1inclusionprocessmales240516.png","url":"https://assets-eu.researchsquare.com/files/rs-4595839/v1/530cf5a63b0b56e84472caec.png"},{"id":60355157,"identity":"265a8404-9ba8-4657-9003-f78e0ffc2b17","added_by":"auto","created_at":"2024-07-16 00:00:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":59074,"visible":true,"origin":"","legend":"\u003cp\u003eMedian BFS scores for (A) patients vs. controls (p \u0026lt;0.001) and (B) per patient age group (p=0.034). (Abbreviations: bowel function score, BFS)\u003c/p\u003e","description":"","filename":"Figure2bfsgrouparmage.png","url":"https://assets-eu.researchsquare.com/files/rs-4595839/v1/3dc085801065d379ce84097a.png"},{"id":60355156,"identity":"5fc3bc75-31b2-4f86-8794-dd6734c0c95c","added_by":"auto","created_at":"2024-07-16 00:00:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":132029,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot comparing BFS outcomes for patients (p=0.008) and controls in relation to increasing age. (Abbreviations: bowel function score, BFS)\u003c/p\u003e","description":"","filename":"Figure3bfsscatterplotage.png","url":"https://assets-eu.researchsquare.com/files/rs-4595839/v1/23f9b81380bbdf1aeb554053.png"},{"id":60354389,"identity":"e7c3354e-1582-4c3e-bb10-130a48055b38","added_by":"auto","created_at":"2024-07-15 23:52:23","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":344069,"visible":true,"origin":"","legend":"\u003cp\u003eRadial diagram of KIDSCREEN-52 and PGWBI cohort mean values per domain compared to normative data. (Abbreviation: Psychological General Well-Being Index, PGWBI)\u003c/p\u003e","description":"","filename":"Figure4radialplot.png","url":"https://assets-eu.researchsquare.com/files/rs-4595839/v1/ac437deff1b7ab947d84af14.png"},{"id":60355537,"identity":"d06a9000-73af-4f28-bbd7-b2d3f460df92","added_by":"auto","created_at":"2024-07-16 00:08:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1245052,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4595839/v1/b6f022d6-2906-42c0-85fa-ae9f38398c14.pdf"},{"id":60354387,"identity":"391dc442-7af4-4040-b132-2647989917bd","added_by":"auto","created_at":"2024-07-15 23:52:23","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14281,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary table 1: \u003c/strong\u003eSample sizes of cohort and controls age groups.\u003c/p\u003e","description":"","filename":"Supplementarytable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4595839/v1/ad26eda78bccd0e77524297f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eBowel Function, Urinary Tract Function, and Health-related Quality of Life in Males With Anorectal Malformations\u003c/p\u003e","fulltext":[{"header":"Highlights","content":"\u003cp\u003e\u003cem\u003e-What is currently known about this topic?\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFunctional and health-related quality of life outcomes into adulthood for males with anorectal malformation (ARM) are still scantily studied.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cem\u003e-What new information is contained in this article?\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHRQoL in male patients is unaffected in our cohort and the negatively impacted bowel function alleviates with increasing age. Also, lower urinary tract function improves with age.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eCongenital anorectal malformations (ARM) are one of many congenital anomalies amongst newborns. The birth prevalence of ARM in Sweden is approximately 1:3000 [1, 2]. There is a small predominance of male infants born with ARM with a sex ratio of 1.3:1 [1]. Associated malformations occurred in 50\u0026ndash;67% patients with ARM in a registry-based study of 17 European regions [3]. It is assumed that associated malformations have a negative impact on overall outcomes of patients with ARM.\u003c/p\u003e \u003cp\u003eClassification of ARM subtypes is essential to correctly treat patients and to facilitate comparative research in national and international settings. Previously, the Wingspread and Pe\u0026ntilde;a classifications were widely used. More recently, the clinically orientated Krickenbeck classification has been adopted[4\u0026ndash;6]. Male anomalies include perineal cutaneous fistula, bulbar rectourethral and prostatic rectourethral, recto bladder-neck vesical fistula, atresias without a fistula as well as anal stenosis.\u003c/p\u003e \u003cp\u003eThe vast majority of ARM patients require corrective surgery in the neonatal period or infancy. Pe\u0026ntilde;a and DeVries introduced the existing surgical techniques, a posterior sagittal anorectoplasty (PSARP), in the early 1980\u0026rsquo;s[7]. Minimally invasive techniques using laparoscopic-assisted anorectoplasty (LAARP) now has a place in the management of selected male ARM patients [8]. The survival rates in infants with ARMs have steadily increased over the years alluding to the progress of surgical and neonatal care. As a result, a shift in treatment goals has occurred from survival to optimizing functional outcomes and preserving a good health-related quality of life (HRQoL). Composite and controlled data for outcomes of bowel function, urinary tract function and quality of life are lacking. Amongst published work, quality of life and bowel function is shown to be impaired in patients with ARM [9\u0026ndash;11] Our group recently investigated these outcomes in female patients[12]. Here, we focus on male patients and aim to assess their outcomes into adulthood in a controlled study-design.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis was cross-sectional questionnaire-based study. The study was registered in ClinicalTrials.gov (NCT04901819).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting\u003c/h2\u003e \u003cp\u003eIndividuals with ARM managed at the Unit of Pediatric Surgery at Karolinska University Hospital, Stockholm, Sweden. In 2024, Sweden has a population of roughly 10.6\u0026nbsp;million persons.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eAll surgically managed males with ARM at our institution between 1994 and 2017 were eligible for the study. A database of identified eligible patients was created. The ARM subtypes which were included were perineal fistulas, rectourethral fistulas (both bulbar and prostatic), recto bladder-neck fistulas as well as atresias without fistulas. Deceased patients and patients without surgical interventions were excluded from the study. In extension, patients with Currarino syndrome, Down\u0026rsquo;s syndrome and patients with major intellectual disabilities were excluded from the study. After informed consent, participants and, or caregivers were asked to answer a composite questionnaire pertaining to the focus of study. Participants had the option to respond using paper mail or a digital platform (REDCap). A reminder was mailed to non-respondents after 4 and 8 weeks, respectively. Age categories (4\u0026ndash;7, 8\u0026ndash;12, 13\u0026ndash;17, 18\u0026ndash;26 years) determined which questionnaires were received. A control group of 2518 healthy age-matched individuals were randomly selected by Statistics Sweden from the Sweden Population Registry and invited to respond to Bowel function score (BFS) and Lower Urinary Tract Symptoms (LUTS) questionnaires. One hundred-ninety-nine (8%) controls responded and 88 of them (44%) were males and thus used for comparison. Normative data were used to compare HRQoL outcomes[13].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData sources and variables\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003ePatient characteristics and clinical details were recorded retrospectively from the medical records. These data included information about associated anomalies, ARM subtype according to Krickenbeck Classification, surgical procedures and age at time of the study. The follow-up date was set to the 15th of June 2021.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003eBowel Function\u003c/h2\u003e \u003cp\u003eBowel function was assessed in all age categories using the previously validated BFS developed in the Finnish population [14, 15]. A BFS score of \u0026ge;\u0026thinsp;17 of maximum 20 was used as an indicator of well-preserved bowel function as described previously by Kyrklund et al. [14]. Bowel function was evaluated in patients regardless of the use of laxatives, enemas, or antidiarrheal medication. No patients included in the cohort had enterostomies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eUrinary Tract Function\u003c/h2\u003e \u003cp\u003eUrinary tract function was examined in all age categories with the validated 9-question Lower Urinary Tract Symptoms (LUTS) questionnaire [16]. Three out of seven items in the employed LUTS questionnaire were based on an adaptation from the previously validated Danish Prostatic Symptom Score [17]. Patients with urinary diversion or who performed clean intermittent catheterization (CIC) were excluded prior to data analysis. Urinary tract function outcomes will be presented descriptively, the major endpoint being the prevalence of urinary incontinence defined as involuntary urinary leakage.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eHealth-Related Quality of Life (HRQoL)\u003c/h2\u003e \u003cp\u003eTo assess children\u0026rsquo;s and adolescents\u0026rsquo; (8 to 17 years old) subjective health and well-being, the KIDSCREEN-52 questionnaire was used as a validated instrument [18, 19]. The instrument covers 10 HRQoL dimensions encompassing Physical Well-being, Psychological Well-being, Moods \u0026amp; Emotions, Self-Perception, Autonomy, Parent Relation \u0026amp; Home Life, Financial Resources, Social Support \u0026amp; Peers, School Environment and Social Acceptance (Bullying). The generic questionnaire is designed for both healthy and chronically ill children, also providing European normative data for comparison in this study [18].\u003c/p\u003e \u003cp\u003eIn adults (18 to 26 years old), the validated instrument Psychological General Well-Being Index (PGWBI) was employed [13, 20, 21]. The instrument includes six dimensions comprising a total of 22 items with a maximal total score of 110, the higher the score the better HRQoL. The dimensions include Anxiety, Depressed Mood, Positive Well-being, Self-Control, General Health, and Vitality. Outcomes of the survey are interpreted as follows; 0\u0026ndash;60 \u0026ldquo;Severe Distress\u0026rdquo;, 61\u0026ndash;71 \u0026ldquo;Moderate Distress\u0026rdquo;, 72\u0026ndash;92 \u0026ldquo;No Distress\u0026rdquo;, and 93\u0026ndash;110 \u0026ldquo;Positive Well-being\u0026rdquo; [21]. A score of roughly 80 is considered a mean score in large reference groups [22, 23]. Normative data for male healthy individuals were used when analyzing PGWBI outcomes.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Methods\u003c/h2\u003e \u003cp\u003eCategorical variables were presented using frequencies and proportions whereas continuous variables were presented as median with interquartile range (IQR) or mean with standard deviation (SD). LUTS and BFS values were compared between patients and age-matched female controls using the Fisher's exact and Wilcoxon Sum Rank Tests, respectively. Trends between age groups and BFS item scores in the patient group were analyzed using Asymptotic Linear-by-Linear Association Test. The overall BFS sum-score was compared between age groups within cases and controls separately using non-parametric test (Jonckheere-Terpstra Test). For LUTS, a logistic regression model comparing patients and controls and adjusting for age as a continuous variable was designed to estimate the Odds (OR) for having any LUTS (defined as presence of at least one symptom).\u003c/p\u003e \u003cp\u003eKIDSCREEN values were translated to T values using the KIDSCREEN instruction manual and compared to European normative data for children \u0026amp; adolescents aged 8\u0026ndash;17 years old using a t-test [10]. Likewise observed PGWBI scores were compared to reference scores using a t-test [13].\u003c/p\u003e \u003cp\u003eThe Spearman correlation test was used to analyze the association between BFS and the HRQoL variables (rho\u0026thinsp;\u0026gt;\u0026thinsp;0.7\u0026thinsp;=\u0026thinsp;strong correlation, \u0026gt; 0.4 moderate association, 0.2\u0026ndash;0.4\u0026thinsp;=\u0026thinsp;no correlation). T-tests were used to analyze relationships between the presence of LUTS and HRQoL variables. A significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was used.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEthical considerations\u003c/h2\u003e \u003cp\u003eThe study was approved by the Swedish Ethical Review Authorities.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003ePatient Characteristics\u003c/h2\u003e\n \u003cp\u003eThe inclusion process is summarized in Fig.\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e. The median age of the included patients and controls at the time of the study was 11 (IQR 7.8) years and 11.5 (IQR 8) years, respectively. One patient had Down syndrome and was thereby excluded from the study. Forty-six responders were 4\u0026ndash;17 years of age and 11 were 18\u0026ndash;26 years of age. The number of individuals included in each age group and their median ages are summarized in Supplementary Table\u0026nbsp;1. Thirty-four (59.6%) patients received a stoma neonatally. A PSARP was performed in 26/57 (45.6%) patients whilst a limited PSARP was employed in 25/57 (43.9%). One child and 5 adult patients had missing data concerning type of primary surgery. Forty percent of the patients had been treated for a perineal fistula and a just over a quarter (25.9%) had had a rectourethral fistula (Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e). Due to lack of specificity in reporting in medical records, the rectobulbar and rectoprostatic urethral fistulas were pooled into one subgroup depicted as rectourethral fistulas. Associated malformations, for those included in the study, were common with 48.3% of patients having one or more associated malformation. VACTERL association was found in 15.5% of patients. Nine patients currently employed anterior continence enemas (ACE).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003ePatient Characteristics of the 58 responders. (Abbreviations: Interquartile range, IQR; anorectal malformation, ARM; antegrade continence enema, ACE; VACTERL, vertebral-anal-cardiac-tracheo-esophageal-renal-limb)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN (%\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMissing Data (n)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian age at follow-up (Years, Median, IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (7.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eType of ARM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePerineal Fistula\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;Rectourethral Fistula\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;Atresia without Fistula\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eRecto Bladder-neck\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eOther (e.g. stenosis)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23 (39.7)\u003c/p\u003e\n \u003cp\u003e15 (25.9)\u003c/p\u003e\n \u003cp\u003e7 (12.1)\u003c/p\u003e\n \u003cp\u003e3 (5.1)\u003c/p\u003e\n \u003cp\u003e3 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAssociated malformations\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eEsophageal atresia\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eCardiac malformation\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eUrinary tract anomalies\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eVertebral anomalies\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eTracheal anomalies\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eLimb abnormalities\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eVACTERL association\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eSpinal cord abnormality\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (48.3)\u003c/p\u003e\n \u003cp\u003e4 (6.9)\u003c/p\u003e\n \u003cp\u003e9 (15.5)\u003c/p\u003e\n \u003cp\u003e12 (20.7)\u003c/p\u003e\n \u003cp\u003e12 (20.7)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2 (3.4)\u003c/p\u003e\n \u003cp\u003e9 (15.5)\u003c/p\u003e\n \u003cp\u003e11 (19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePermanent stoma at follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntegrade Continence Enema (ACE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePermanent Urinary Diversion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurrent Occupation among patients\u0026thinsp;\u003cspan type=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;18 years, n\u0026thinsp;=\u0026thinsp;12\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eStudent\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eFull-time employed\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ePart-time employed\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eOn sick-leave\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (50.0)\u003c/p\u003e\n \u003cp\u003e3 (25.0)\u003c/p\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUse of laxatives or enemas excluding ACE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eChildren and Adolescents\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eAdults\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (54.3)\u003c/p\u003e\n \u003cp\u003e5 (41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003eBowel Function Score\u003c/h2\u003e\n \u003cp\u003eNo patients had a permanent enterostomy at the time of the study. Patients with ACE were included in the analysis. The median BFS for patients was 16 (IQR 5) compared to 19 (IQR 1) for controls (Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003eA) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Due to missing values in the control responses 85/88 controls could be used for data analysis. Differences in Median BFS scores between age groups within the cohort were statistically significant (Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003eB and \u003cspan\u003e3\u003c/span\u003e). Both a non-parametric test (Jonckheere-Terpstra Test) and a linear regression model showed statistically significant increases in BFS with age, with p-values of 0.034 and 0.008, respectively. For every additional year of age, BFS is shown to increase 0.22 arbitrary units. A well-preserved bowel function defined as BFS\u0026thinsp;\u0026ge;\u0026thinsp;17 of 20 was found in 42.1% (24/57) of patients compared to 95.3% (81/85) in controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fischer\u0026rsquo;s exact test). In the patient cohort, 37.0% (17/46) of children and adolescents and 63.6% (7/11) of adults reported a well-preserved bowel function.\u003c/p\u003e\n \u003cp\u003eThe patients reported statistically significant lower scores across all items in the questionnaire when compared to the control group, except for their defecation frequency, displayed in Table\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBowel Function Scores per item and age groups, comparing cohort and controls. * Fishers Exact Test. (Abbreviations: Interquartile range, IQR; Bowel Function Score, BFS)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eItem Score\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCohort, n (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eControls, n (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value*\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.33 (6.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.15 (5.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.846\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eAge group 4\u0026ndash;7 years\u003c/p\u003e\n \u003cp\u003e8\u0026ndash;12 years\u003c/p\u003e\n \u003cp\u003e13\u0026ndash;17 years\u003c/p\u003e\n \u003cp\u003e18\u0026ndash;26 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.957\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (36.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32 (36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (21.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eFeels/reports the urge to defecate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 ( 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 ( 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 ( 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 ( 5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (59.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81 (92.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eAbility to hold back defecation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 ( 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 ( 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (26.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 ( 3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (49.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83 (94.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eFrequency of defecation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.182\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44 (77.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75 (86.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eSoiling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 ( 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 ( 0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 ( 2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64 (73.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eAccidents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 ( 1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 ( 0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 ( 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 ( 0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 ( 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (71.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84 (95.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eConstipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 ( 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (28.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 ( 2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (36.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73 (83.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eSocial problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 ( 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 ( 0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 ( 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 ( 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40 (70.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86 (97.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBFS score (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.00 [13.00, 18.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.00 [19.00, 20.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eBFS\u0026thinsp;\u0026ge;\u0026thinsp;17/20, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (57.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 ( 4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u0026ndash;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (42.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81 (95.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eA linear-by-linear asymptotic association test was used and suggested statistically significant trends in 2 of the 7 BFS-items. A positive trend was seen in the \u0026lsquo;feels urge\u0026rsquo; item where it improved with increasing age group (p\u0026thinsp;=\u0026thinsp;0.026). Further, a positive trend was seen in \u0026lsquo;soiling\u0026rsquo; where this issue mitigated with increasing age group (p\u0026thinsp;=\u0026thinsp;0.001). No other significant trends were identified relating to individual BFS-items and age.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\"\u003e\n \u003ch2\u003eUrinary Tract Function\u003c/h2\u003e\n \u003cp\u003eOne child and one adult, both having sacral dysgenesis, used CIC and were excluded from this analysis. The sense of urgency and the need to strain were the most common symptoms in the cohort with 17.2% and 16.3%, respectively, having these symptoms to some degree. For the controls, bedwetting was the most common symptom reported with a percentage of 11.3. Fishers Exact Test was performed to compare age group distribution and overall LUTS prevalence between patient and controls, no statistical differences (p\u0026thinsp;=\u0026thinsp;0.975 and p\u0026thinsp;=\u0026thinsp;0.299, respectively) were observed. However, the estimated Odds Ratio for having LUTS (LUTS\u0026thinsp;\u0026gt;\u0026thinsp;0) as a patient was 1.8 times higher than for controls (95% CI 0.85, 3.83). Stress incontinence and straining during urination were significantly higher in the cohort (p\u0026thinsp;=\u0026thinsp;0.031 and 0.007, respectively). Bedwetting in the cohort was reported marginally more frequently, p\u0026thinsp;=\u0026thinsp;0.050. Including spontaneous leakage, as a measure of voiding incontinence, no other factors were significantly different between patients and controls. No adult patients in the cohort reported stress incontinence, urge incontinence, bedwetting, social problems due to incontinence or spontaneous leakage.\u003c/p\u003e\n \u003cp\u003eIn patients and controls, both the prevalence of having symptoms and the number of cumulative symptoms drop with increasing age. A logistic regression model using age as a continuous variable showed that the odds (OR) decreases for LUTS 0.87 times (95% CI 0.80, 0.93) for every additional year of age (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\"\u003e\n \u003ch2\u003eHRQoL\u003c/h2\u003e\n \u003cdiv id=\"Sec18\"\u003e\n \u003ch2\u003eKIDSCREEN for children and adolescents\u003c/h2\u003e\n \u003cp\u003eVisually, the normalized mean domain T-values in the cohort did not differ significantly from the age- and gender-matched European normative data (Fig.\u0026nbsp;\u003cspan\u003e4\u003c/span\u003e). Paradoxically, cohort patients had a significantly higher score in the Financial Resources, Parent Relations, School Environment and Bullying social acceptance domains (p\u0026thinsp;=\u0026thinsp;0.000, 0.026, 0.002, 0.001, respectively).\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\"\u003e\n \u003ch2\u003ePGWBI for adults\u003c/h2\u003e\n \u003cp\u003eThe mean normalized PGWBI for the cohort was 81.3 compared to the reference data having a mean score of 73.9 (p\u0026thinsp;=\u0026thinsp;0.002). Table\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e summarizes the cohort and normative data per domain. The cohort scored significantly higher in several domains including \u0026lsquo;Anxiety\u0026rsquo; and \u0026lsquo;General Health\u0026rsquo;. The cohort did not score inferiorly to the norm data in any domain, graphically visualized in Fig.\u0026nbsp;\u003cspan\u003e4\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003ePGWBI domain scores compared to norm data. (Abbreviation: Psychological General Well-Being Index, PGWBI)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePGWBI Domain\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCohort, Mean (SD)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNormative Data, Mean (SD)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnxiety\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80.0 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71.4 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDepressed mood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88.7 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e84.2 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGeneral Health\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89.3 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77.2 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive Well-being\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72.5(12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.1 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSelf Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88.7(9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82.5 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVitality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74.5(10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68.3 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndex Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81.3 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73.9 (15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003c/div\u003e\n \u003cp\u003eOne patient scored within the \u0026ldquo;severe distress\u0026rdquo; bracket (0\u0026ndash;60 points). This patient also utilized CIC and had the poorest BFS (13/20) of the adult group. Eight patients (72.7%) had \u0026ldquo;no distress\u0026rdquo; (72\u0026ndash;92) and two patients (18.2%) reported \u0026ldquo;being positive\u0026rdquo; (72\u0026ndash;110). None of the adult patients were on sick leave at follow-up time and 90.9% of them did not subjectively feel that their choice of occupation was affected by their ARM (Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\"\u003e\n \u003ch2\u003eComposite Outcomes\u003c/h2\u003e\n \u003cdiv id=\"Sec21\"\u003e\n \u003ch2\u003eKIDSCREEN and BFS\u003c/h2\u003e\n \u003cp\u003eA Spearman correlation test (Rho\u0026thinsp;=\u0026thinsp;\u0026rho;) was performed to evaluate correlation between KIDSCREEN item T-scores and BFS. Overall, no correlations could be found except for the patient\u0026rsquo;s autonomy (\u0026rho;\u0026thinsp;=\u0026thinsp;0.525, \u0026gt;\u0026thinsp;0.4\u0026thinsp;=\u0026thinsp;moderate correlation) and financial aspects (\u0026rho;\u0026thinsp;=\u0026thinsp;0.442). There is therein a moderate association between a higher BFS and better subjective autonomy and their perceived financial situation.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec22\"\u003e\n \u003ch2\u003eKIDSCREEN and LUTS\u003c/h2\u003e\n \u003cp\u003eAssuming that KIDSCREEN T-values have a normal distribution, a T-test was used to see if a relation was present between KIDSCREEN items and the presence of LUTS (excluding history of UTI). No associations were found.\u003c/p\u003e\n \u003cdiv id=\"Sec23\"\u003e\n \u003ch2\u003ePGWBI, LUTS and BFS\u003c/h2\u003e\n \u003cp\u003eThe relationships of PGWBI contra LUTS and BFS were analyzed, however, no associations could be shown.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec24\"\u003e\n \u003ch2\u003eARM-subtype and BFS\u003c/h2\u003e\n \u003cp\u003eThe subtype groups for perineal (n\u0026thinsp;=\u0026thinsp;21) and rectourethral (n\u0026thinsp;=\u0026thinsp;14) fistulas in children and adolescents were large enough to analyze where 62% and 14% had a BFS\u0026thinsp;\u0026ge;\u0026thinsp;17/20, respectively (Exact test p\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec26\" class=\"Section2\"\u003e \u003ch2\u003eKey Findings\u003c/h2\u003e \u003cp\u003eThe bowel function of males treated for ARM was grossly impaired across all age groups when compared to healthy controls. For the cohort, 42.1% reported an acceptable bowel function compared to 95.3% in the controls. Bowel function in the cohort improved with 0.22 units per year of age and 63.6% of adult patients reported a BFS of \u0026ge;\u0026thinsp;17/20. Soiling issues and the ability to feel the urge to defecate improved significantly in the cohort with increasing age group. Contrarily to findings by Rintala et al and our previous study on females, constipation issues did not change with increasing age [12, 24]. Voiding outcomes in general were comparable to the controls. Nonetheless, LUTS were more common in the ARM group compared to the controls. The OR decreases for LUTS 0.87 times for every additional year of age. The sense of urgency and the need to strain to urinate were the most common LUTS in the cohort. Involuntary leakage did not occur in any of the adult patients in the study. In accordance with a recent systematic review showing a high LUTS prevalence (36%) 10-years after surgical repair, 41.8% of patients in our cohort had at least one LUTS [25]. Our data is in the middle range of what has been reported in the literature (18\u0026ndash;72%) [25, 26]. The recent review article describes a UTI rate of 36.4% compared to 13% in our cohort [26].\u003c/p\u003e \u003cp\u003eIn accordance with previous results, HRQoL was preserved with children and adolescents in this cohort [12, 27]. Surprisingly, the cohort scored significantly higher in the domains of Financial Resources, Parent Relations, School Environment and Bullying social acceptance. Further, an association was found between BFS and the children\u0026rsquo;s feelings of autonomy and their financial perceptions. Regarding autonomy, this relation was recently described even for female ARM patients in our previous study [12]. Hypothetically, an acceptable bowel function could influence autonomy, not having to ask for help or assistance if, for example, fecal accidents happen. In the adult group, the HRQoL was preserved and paradoxically scored higher on the overall score when compared to normative data. Nearly three-quarters of patients reported \u0026ldquo;no distress\u0026rdquo; which is the same category where the mean result (80) is found in large reference groups [23]. The PGWBI scores could not be associated statistically to either LUTS or BFS.\u003c/p\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eInterpretation\u003c/h2\u003e \u003cp\u003eThrough literature review, few studies have focused on gender-specific outcomes after surgical repair of ARM while comparing them to matched controls. In extension to our previous research, \u0026ldquo;partially pertaining to anatomical differences, the phenotypes of the malformations differ between males and females and thus should be studied separately\u0026rdquo;[12]. Studying the genders separately has suggested major differences in the two groups. In males, BFS and LUTS improved with increasing age and even adult patients had a preserved HRQoL. This was not the case for our female cohort [12].\u003c/p\u003e \u003cp\u003eChoosing a suitable questionnaire was crucial for this study. The multivariate BFS by Rintala et al was employed to facilitate comparison of outcomes between present and future ARM studies [15]. Through literature review, BFS has been trending in recent years. Further, geographically neighboring Nordic countries, having similar sociocultural-economic structures and health care systems are deemed to be comparable on the population general health level [14]. This study confirms previously published results reporting bowel function impairment in ARM patients [28]. In this study 42.1% of patients had acceptable bowel function, a figure substantially higher than what we previously reported for females (32.6%) from the same center and time period [12]. This points to the heterogeneity of the malformation and gender-specific differences.\u003c/p\u003e \u003cp\u003eA mean BFS of 15.1 (SD 4.0) in our study is comparable to 13.9 found by Kaselas et al, although Kaselas pooled females and males together. ARM subtype is of interest in relation to BFS, however, our cohort was too small to yield substantial power for most subgroup analyses. However, we found that perineal fistulas in children had better bowel function outcomes compared to children with recto-urethral fistulas. In 2005, Levitt and Pe\u0026ntilde;a concluded that constipation was the most common complication in patients who had undergone PSARP [29]. Second to soiling issues reported in 64.9% of our cohort, 63.2% of patients had some degree of constipation.\u003c/p\u003e \u003cp\u003eInterpreting HRQoL of patients with congenital malformations is a challenge. For example, these patients were born with their condition and thereby their reference of HRQoL could arguably differ from that of the reference population. In children and adolescents in this study, their reported HRQoL was not inferior to the normalized reference data. In fact, our cohort scored higher on several items. These findings are in par with results reported by Wigander et al from a Swedish cohort of children with low ARM where patients and controls had comparable HRQoL (HAQL tool) [30]. A recently published paper by Beattie et al found conflicting results to ours where they used the PedsQL tool showing significantly impaired quality of life in children[31]. Further, Beattie et al reported no differences in QoL between genders in children with ARM. HRQoL studies performed by Hartmann et al show a large variation in quality of life in patients treated for ARM[32]. Patients doing very poorly are an urge for concern and must be identified early on by clinicians to implement extra care[33]. \u0026Ouml;rtqvist et al recently reported in a multi-center Nordic study that even patients operated on for a cloacal malformation had similar HRQoL compared to healthy a Swedish Population [34]. Critical comparison of studies is made difficult due to study design differences as well as the use of different investigating tools. Few studies have focused on the span of ages into adulthood for males regarding HRQoL and there lies no consensus for which HRQoL tool should be used. For our purposes, the KIDSCREEN tool was suitable as it has been broadly used in the Nordic setting and has normative data on a large scale.\u003c/p\u003e \u003cp\u003eIn adult males from this cohort, their HRQoL was not either found be inferior to normative European data. Published work on this topic with similar cohorts is scanty. A thirty-year-old paper by Hassink et al looking at 58 adults having been operated for a high ARM observed that \u0026ldquo;most aspects of QoL and mental health did not differ from those of the general population\u0026rdquo; [35]. It could be speculated that coming into puberty and adulthood leading to sexual debut could lead to impaired HRQoL. However, this does not seem to be the case in our cohort.\u003c/p\u003e \u003cp\u003eComposite outcomes in this setting have been scantily studied to this point. We aimed to analyze potential associations between HRQoL, bowel function and urinary tract function. Parallelly to the previously published female cohort, BFS is even shown to be associated to the feeling of autonomy in male children [12]. Further, male children and adolescents\u0026rsquo; BFS correlates moderately to the financial resources item of HRQoL. These aspects are assumed to be influenced by several variables which is why the associations found were moderate. Children with perineal fistulas statistically had better bowel function outcomes than children with rectourethral fistulas. This is in par with previous research where higher, more complex malformations have been shown to have impaired bowel continence [31, 36, 37].\u003c/p\u003e \u003cp\u003eIn general, the relatively small groups of patients and large number of variables make these analyses challenging. Furthermore, certain analyses which had been envisioned were unable to be carried out. For example, we collected data on spinal and other associated anomalies, however, the amount of missing data proved to be too large to yield generalizable results (data not published). Overall, the same applies for the influence that ARM-subtype might have on BFS, LUTS and HRQoL.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eTo reduce confounding factors, the heterogenicity of the cohort was limited. Selection bias of the responders was minimal as potential participants met the inclusion criteria before asked to answer the questionnaires. Yet, it is possible that patients in need of medical attention have a greater inclination to participate which would create a selection bias. A first limitation was the sample size. Our intended secondary aim to examine long-term outcomes per ARM-subtype proved difficult to answer due to the low response rate (44.6%) subsequentially making subgroups too small to generate statistical power concerning certain issues. Additionally, the response rate in the control group was likewise low. A second limitation involves the presence of ongoing treatments with laxatives and, or antidiarrheal medications, which the healthy controls were not exposed to.\u003c/p\u003e \u003cp\u003eA third and final limitation is the cross-sectional study design. Not having followed a specific patient over time, it is difficult to evaluate changes in outcomes over time. For instance, we cannot conclude that a specific ARM patients\u0026rsquo; BFS improves with age, although there is a general difference between age groups. We can, however, indicate that even LUTS prevalence decreases with increasing age and that HRQoL is preserved in all ages. Another factor potentially influencing outcomes if the heterogenicity of ARM-subtype complexity per age group. As the number of individuals with a specific subtype varied per age group, this could represent a confounding factor when interpreting results. A causality relationship between HRQoL and the congenital malformation could not be shown in this study. HRQoL is multifactorial and the response-shift umbrella concept should always be considered when interpreting HRQoL data [38].\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eRoughly 40% of the male ARM patients reported well-preserved bowel function, a function that improved with age. LUTS prevalence diminished with age and no adults had involuntary urinary leakage, however, it must be noted that patients using CIC were excluded. Neither children nor adults were found to have an inferior HRQoL when compared to norm European data. Composite variable analysis proved difficult. These findings confirm the importance of transitioning male adolescents to adult care that can provide expertise in the sequelae of anorectal malformations.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cem\u003eACE- Antegrade Continence Enema\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eARM- Anorectal Malformation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBFS- Bowel Function Score\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCI- Confidence Interval\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCIC- Clean Intermittent Catheterization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHRQoL- Health-Related Quality of Life\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIQR- Interquartile Range\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePGWBI- Psychological General Well-Being Index\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePSARP- Posterior Sagittal Ano-Recto-Plasty\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLAARP- Laparoscopically Assisted Ano-Recto-Plasty\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLUTS- Lower Urinary Tract Symptoms\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSD- Standard Deviation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eUTI- Urinary Tract Infection\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVACTERL- vertebral-anal-cardiac-tracheo-esophageal-renal-limb\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFinancial Support Statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has been supported by grants from Kronprinsessan Lovisa\u0026rsquo;s F\u0026ouml;rening f\u0026ouml;r Barnasjukv\u0026aring;rd, S\u0026auml;llskapet Barnav\u0026aring;rd, Barnforskningen from the Astrid Lindgren Children\u0026rsquo;s Hospital, and Birgitta and Carl-Axel Rydbeck Research Grant for Pediatric Research.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e\u003cu\u003eAuthor Contribution Form (*)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eType the name of each author next to the appropriate following categories:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStudy conception and design: JG, L\u0026Ouml;, TW\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData acquisition: JG, L\u0026Ouml;, ALG\u003c/p\u003e\n\u003cp\u003eAnalysis and data interpretation: JG, L\u0026Ouml;, TW\u003c/p\u003e\n\u003cp\u003eDrafting of the manuscript: JG, L\u0026Ouml;, TW\u003c/p\u003e\n\u003cp\u003eCritical revision: L\u0026Ouml;, TW, ALG, JO, AG, AS\u003c/p\u003e\n\u003cp\u003eSubmit this form with the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has been made possible by grants from Kronprinsessan Lovisa\u0026rsquo;s F\u0026ouml;rening f\u0026ouml;r Barnasjukv\u0026aring;rd, S\u0026auml;llskapet Barnav\u0026aring;rd, Barnforskningen from the Astrid Lindgren Children\u0026rsquo;s Hospital and Birgitta and Carl-Axel Rydbeck Research Grant for Pediatric Research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Eva Hagel for her valued statistical support and our patients for their participation. We also thank Gustav Stenkvist for his help with initial data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of generative AI and AI-assisted technologies in the writing process\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eArtificial Intelligence (AI) and AI-assisted technologies were not used in the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e(*): Modified from the authorship requirements of the J Am Coll Surg\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eDisclosure:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no actual or potential conflict of interest in relation to this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSvenningsson A, Gunnarsdottir A, Wester T (2018) Maternal risk factors and perinatal characteristics of anorectal malformations. J Pediatr Surg 53(11):2183-8.\u003c/li\u003e\n\u003cli\u003eKancherla V, Sundar M, Tandaki L, Lux A, Bakker MK, Bergman JE, et al (2023) Prevalence and mortality among children with anorectal malformation: A multi-country analysis. Birth Defects Res 115(3):390-404.\u003c/li\u003e\n\u003cli\u003eWijers CH, van Rooij IA, Bakker MK, Marcelis CL, Addor MC, Barisic I, et al (2013) Anorectal malformations and pregnancy-related disorders: a registry-based case-control study in 17 European regions. BJOG 120(9):1066-74.\u003c/li\u003e\n\u003cli\u003eStephens FD SE (1986) Classification, identification and assessment of surgical treatment of anorectal anomalies. Pediatr Surg Int 1: 200-205.\u003c/li\u003e\n\u003cli\u003ePena A (1995) Anorectal malformations. 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Scand J Urol Nephrol 1993;27(4):489-92.\u003c/li\u003e\n\u003cli\u003eRavens-Sieberger U (2006) The KIDSCREEN questionnaires-Quality of life questionnaires for children and adolescents-Handbook. Pabst Science Publishers, Lengerich. 3rd edition 2016. \u003c/li\u003e\n\u003cli\u003eRavens-Sieberer U, Herdman M, Devine J, Otto C, Bullinger M, Rose M, et al (2014) The European KIDSCREEN approach to measure quality of life and well-being in children: development, current application, and future advances. Qual Life Res 23(3):791-803.\u003c/li\u003e\n\u003cli\u003eDupuy HJ. Edited by Wenger NK MM, Furberg CD, Elinson J (1984) The Psychological general Well-Being (PGWB) Index. 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Int J Colorectal Dis 26(3):351-6.\u003c/li\u003e\n\u003cli\u003eLevitt MA, Pena A (2005) Outcomes from the correction of anorectal malformations. Curr Opin Pediatr 17(3):394-401.\u003c/li\u003e\n\u003cli\u003eWigander H, Nisell M, Frenckner B, Wester T, Brodin U, Ojmyr-Joelsson M (2019) Quality of life and functional outcome in Swedish children with low anorectal malformations: a follow-up study. Pediatr Surg Int 35(5):583-90.\u003c/li\u003e\n\u003cli\u003eBeattie H, Subramanian T, Scudamore E, Middleton T, MacDonald C, Lindley R, et al (2024) Assessment of long-term quality of life, bowel and voiding function outcomes in patients with anorectal malformation at a single UK centre. Pediatr Surg Int 40(1):95.\u003c/li\u003e\n\u003cli\u003eHartman EE, Oort FJ, Aronson DC, Hanneman MJ, van Heurn E, de Langen ZJ, et al (2007) Explaining change in quality of life of children and adolescents with anorectal malformations or Hirschsprung disease. Pediatrics 119(2):e374-83.\u003c/li\u003e\n\u003cli\u003eHartman EE, Oort FJ, Sprangers MA, Hanneman MJ, van Heurn LW, de Langen ZJ, et al (2008) Factors affecting quality of life of children and adolescents with anorectal malformations or Hirschsprung disease. J Pediatr Gastroenterol Nutr 47(4):463-71.\u003c/li\u003e\n\u003cli\u003eOrtqvist L, Holmdahl G, Borg H, Bjornland K, Lilja H, Stenstrom P, et al (2023) Bowel Control, Bladder Function, and Quality of Life in Children with Cloacal Malformations. J Pediatr Surg 58(10):1942-8.\u003c/li\u003e\n\u003cli\u003eHassink EA, Rieu PN, Brugman AT, Festen C (1994) Quality of life after operatively corrected high anorectal malformation: a long-term follow-up study of patients aged 18 years and older. J Pediatr Surg 29(6):773-6.\u003c/li\u003e\n\u003cli\u003eGoyal A, Williams JM, Kenny SE, Lwin R, Baillie CT, Lamont GL, et al (2006) Functional outcome and quality of life in anorectal malformations. J Pediatr Surg 41(2):318-22.\u003c/li\u003e\n\u003cli\u003eLevitt MA, Pena A (2007) Anorectal malformations. Orphanet J Rare Dis 2:33.\u003c/li\u003e\n\u003cli\u003eBlome C, Augustin M (2015) Measuring change in quality of life: bias in prospective and retrospective evaluation. Value Health 18(1):110-5.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-surgery-international","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pesi","sideBox":"Learn more about [Pediatric Surgery International](http://link.springer.com/journal/383)","snPcode":"383","submissionUrl":"https://submission.nature.com/new-submission/383/3","title":"Pediatric Surgery International","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"anorectal malformation, adulthood, bowel function, urinary tract function, QoL, surgery","lastPublishedDoi":"10.21203/rs.3.rs-4595839/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4595839/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThere is a knowledge gap regarding long-term outcomes for males undergoing surgery for an anorectal malformation (ARM). The purpose of this study was to investigate bowel function, bladder function and health-related quality of life (HRQoL) in male patients with an anorectal malformation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis cross-sectional questionnaire-based study included males treated for ARM at our institution between 1994 and 2017. Bowel function was assessed with bowel function score (BFS) whilst urinary tract function was assessed with Lower Urinary Tract Symptoms (LUTS) questionnaires. Health-related quality of life (HRQoL) was investigated using age-relevant questionnaires (KIDSCREEN and PGWBI). Patient characteristics were retrospectively collected from the medical records and descriptive statistics were used for analysis. Functional outcomes were compared with gender and age-matched controls whilst HRQoL was compared to normative data. The study was approved by ethics review authorities.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 58 (44.6%) of 130 males responded to the questionnaires. Regarding bowel function, twenty-four (42.1%) of 57 patients and 81 (95.3%) of 85 controls, respectively, reported a well-preserved bowel function represented by a BFS\u0026thinsp;\u0026ge;\u0026thinsp;17 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Soiling issues and \u0026lsquo;feels urge\u0026rsquo; items improved significantly with age. In a linear regression model, BFS increased significantly with age. For most parameters, the proportion of ARM patients with lower urinary tract symptoms was larger, though not significantly, compared to the controls. However, straining and stress incontinence were reported significantly more often by ARM patients. In patients and controls, voiding outcomes in terms of prevalence of having symptoms and the number of cumulative symptoms drop with increasing age. Children and adults reported similar or, in some domains, better HRQoL outcomes when compared to normative European data.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBowel function is impaired in male patients with ARM but significantly improves with age. Urinary tract function was affected, but overall comparable to the controls. HRQoL was unaffected. No significant association between the studied outcomes could be shown.\u003c/p\u003e","manuscriptTitle":"Bowel Function, Urinary Tract Function, and Health-related Quality of Life in Males With Anorectal Malformations","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-15 23:52:18","doi":"10.21203/rs.3.rs-4595839/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2024-06-18T10:12:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-18T10:12:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"340165079514415562491512844803786995236","date":"2024-06-18T10:10:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-18T10:06:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-18T10:01:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-18T06:56:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Surgery International","date":"2024-06-17T19:11:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-surgery-international","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pesi","sideBox":"Learn more about [Pediatric Surgery International](http://link.springer.com/journal/383)","snPcode":"383","submissionUrl":"https://submission.nature.com/new-submission/383/3","title":"Pediatric Surgery International","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8f6a1f58-36f6-4d6d-be0e-0e71f92c24d5","owner":[],"postedDate":"July 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-07-15T23:53:16+00:00","versionOfRecord":{"articleIdentity":"rs-4595839","link":"https://doi.org/10.1007/s00383-024-05746-5","journal":{"identity":"pediatric-surgery-international","isVorOnly":false,"title":"Pediatric Surgery International"},"publishedOn":"2024-06-27 23:53:15","publishedOnDateReadable":"June 27th, 2024"},"versionCreatedAt":"2024-07-15 23:52:18","video":"","vorDoi":"10.1007/s00383-024-05746-5","vorDoiUrl":"https://doi.org/10.1007/s00383-024-05746-5","workflowStages":[]},"version":"v1","identity":"rs-4595839","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4595839","identity":"rs-4595839","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}