Prospective study on the incidence of bladder/cloacal exstrophy and epispadias in Europe

doi:10.1016/j.jpurol.2015.03.023

Journal of Pediatric Urology

Volume 11, Issue 6, December 2015, Pages 337.e1-337.e6

https://doi.org/10.1016/j.jpurol.2015.03.023 Get rights and content

Summary

Objective

On behalf of the European Society of Paediatric Urology (ESPU), a prospective study was designed with the aim of defining the actual number of babies born with bladder exstrophy, cloacal exstrophy, and epispadias in Europe over a 12-month period, and verifying the distribution of the exstrophy patients born during the study period among the different paediatric urology centres in Europe.

Study design

The study was structured with a chief investigator and one national investigator for each country enrolled in the study. The national investigators nominated one local investigator for each European centre of paediatric surgery/paediatric urology and urology where the exstrophy complex could potentially be treated. The local investigators were responsible for reporting babies treated in their institutions for bladder/cloacal exstrophy and/or epispadias. During 2010, every 3 months, an electronic survey (Figure) was e-mailed to the local investigators asking them to report babies treated or referred for treatment during the previous 3 months.

Results

One-hundred and sixteen centres in 27 European counties were enrolled in the study. The overall response rate for the four online surveys was 79%. Two-hundred and thirty-eight babies were reported to be born with a condition within the bladder exstrophy epispadias complex (BEEC): 71 primary epispadias (66 males), 146 classic bladder exstrophy (97 males) of which two were female bladder exstrophy variant, and 21 cloacal exstrophy (17 males). Two of 67 (3%) male epispadias, 24/146 (16.4%) bladder exstrophy, and 6/21 (28%) cloacal exstrophy were antenatally diagnosed. Associated anomalies were reported in 2/71 (2.8%) epispadias patients, 8/146 (5.5%) bladder exstrophy patients, and 15/21 (71.4%) cloacal exstrophy patients. One-hundred and forty-seven (62%) of the 238 babies born in Europe with a condition within the exstrophy spectrum during 2010 were transferred from other institutions for treatment (36 male epispadias, 97 bladder exstrophy, and 14 cloacal exstrophy). Only 12 centres treated six or more exstrophy and or epispadias patients during the study period; 52 treated between one and five patients, of which 22 treated only one case in 12 months.

Discussion

This study provides a contemporary incidence of the BEEC in Europe. It demonstrates also that only a minority (19%) of the European centres involved in the treatment of exstrophy can be considered “high volume” exstrophy centres.

Conclusion

There is a case for proposing a rationalisation of the treatment of this group of conditions in a small number of exstrophy units around Europe.

Introduction

According to Eurostat, 5 421 000 live births were registered in the EU27 in 2008 [1]. Considering the published incidence of the bladder exstrophy complex (male epispadias 1:117 000 [2]; female epispadias 1:484 000 [2]; classic bladder exstrophy 1:37 000 [3]; cloacal exstrophy 1:200 000 [4]) in the EU27 every year, about 146 classic bladder exstrophy, 46 male epispadias, 27 cloacal exstrophy, and 11 female epispadias patients would have been expected to be born. Routine antenatal screening ultrasound is commonly used in most European countries. The EUROSCAN study [3] was conducted in 12 European countries between 1996 and 1998 monitoring over 709 000 births. Fifty-two per cent of the bladder exstrophy cases were antenatally detected. The study showed that 80% of the antenatally detected cases of bladder exstrophy were terminated, the incidence of bladder exstrophy in Europe was 1:37 000 foetuses, but only one baby every 71 000 was actually born. What is the incidence of the exstrophy complex in Europe at the moment? Also, what is the average exposure of European paediatric urologists to exstrophy? Is there a need for promoting centralisation of treatment of exstrophy throughout Europe, as has already been adopted in the UK and the Netherlands?

To address these questions, the authors have organised, on behalf of the European Society of Paediatric Urology (ESPU), a prospective study, the aim of which was to define the actual number of babies born with bladder exstrophy, cloacal exstrophy, and epispadias in Europe over a 12-month period and to verify the distribution of the exstrophy patients born during the study period among the different paediatric urology centres in Europe. The study did not investigate the rate of termination of pregnancy when antenatal diagnosis was made.

Section snippets

Methods

The study was announced at the European Society of Paediatric Urology (ESPU) annual meeting in 2007 [5].

It was structured with a chief investigator (RMC), one national investigator for each country enrolled in the study, and a local investigator for each centre enrolled in the study.

The national investigators were selected using primarily the ESPU members' database. For countries where more than one ESPU member was available, the national investigator was chosen based on perceived academic

Results

Twenty-nine countries were invited to take part in the study. No national investigators accepted this role for Ireland and Norway; therefore these two countries were excluded from the study. Twenty-seven national investigators were enrolled in the study in 27 countries in Europe and surrounding areas; the list of the national investigators can be found at http://www.espu.org/be_study/index.php?id=44. One-hundred and seventy local investigators were identified and 116 agreed to take part in the

Discussion

This study confirms the data from Goyal et al. [10] who found an antenatal diagnosis rate of 25% in the BE and CE conditions. Termination of pregnancy is still often advised when BE is detected antenatally [3]; however, because exstrophy can be detected antenatally in only a minority of the cases, the incidence of BE in Europe is similar to the data previously published [2].

Rickham reported an incidence of bladder exstrophy in the Liverpool region (UK) of 1/40 000 between 1942 and 1953, and

Conclusion

This first prospective epidemiological study focused on the bladder exstrophy complex in Europe provides a contemporary incidence of the BEEC. The study demonstrated also that only a minority of the European Paediatric Urology Centres can be considered “high volume” exstrophy units. Considering the need for an experienced multidisciplinary team for the optimal treatment of exstrophy, there is a strong case for proposing a rationalisation of the treatment of this group of conditions in a small

Conflict of interest

None.

Funding

None.

Acknowledgments

The Authors would like to express their gratitude to Mr Clément Ekstein, ESPU webmaster, for his IT support before, during, and after the study period; Mr Manfred te Grotenhuis, Department of Sociology, Radboud University Nijmegen, the Netherlands, for the statistical advise; Prof Sedar Tekgül for supporting the study; all the National and Local investigators for their precious contribution.

References (18)

A. Wiesel et al.
Prenatal Detection of congenital Renal Malformation by Fetal Ultrasonographic Examination: an analysis of 709,030 births in 12 European countries
Eur J Med Genet
(2005)
A. Goyal et al.
Antenatal diagnosis of bladder/cloacal exstrophy: challenges and possible solutions
J Pediatr Urol
(2012)
E. Shapiro et al.
The inheritance of the exstrophy-epispadias complex
J Urol
(1984)
C. Nelson et al.
Contemporary epidemiology of bladder exstrophy in the united states
J Urol
(2005)
Eurostat. http://epp.eurostat.ec.europa.eu/cache/ITY_PUBLIC/3-03082009-AP/EN/3-03082009-AP-EN.PDF [accessed...
J.P. Gearhart et al.
Exstrophy of the bladder, epispadias, and other bladder anomalies
International Clearinghouse for Birth Defects Monitoring Systems
Epidemiology of bladder exstrophy and epispadias: a communication from the international clearinghouse for birth defects monitoring systems
Teratology
(1987)
ESPU....
Eurostat. http://epp.eurostat.ec.europa.eu/cache/ITY_PUBLIC/3-01042011-BP/EN/3-01042011-BP-EN.PDF [accessed...

There are more references available in the full text version of this article.

Cited by (49)

Outcomes From Colonic Pull-Through for Cloacal Exstrophy Differ by Colon Length: A Multi-Institutional Study
2024, Journal of Pediatric Surgery
Cloacal exstrophy (CE) represents a rare sub-group of anorectal malformations. Traditionally managed with a permanent colostomy, colonic pull-through (PT) has emerged to allow cleanliness without a life-long stoma. We sought to understand outcomes of PT in a large multi-center CE population.
We performed a retrospective study involving eleven pediatric hospitals. We gathered data on demographics, outcomes, and anatomical factors including colon length. Continuous variables were analyzed with Wilcoxon rank-sum tests and categorial variables with Fisher's exact tests.
There were 98 patients, of which the majority (n = 70, 71.4 %) never underwent PT. There were no differences in exstrophy type, demographics, or associated anomalies. Median age at PT was 1.3 years (IQR 0.3–3.7). Of the cohort that continue to use their PT, the majority (n = 16, 69.6 %) are not clean. In total, 7.1 % (n = 7) of the cohort is clean with a PT, and only one patient is continent. Clean patients have a longer colon length than those who are not clean or opt for re-do ostomy (64.0 cm [IQR 46.0–82.0] vs 26.5 cm [IQR 11.6–41.2], p = 0.005).
Overall, we demonstrate that most children born with CE will keep their stoma. Only a small percentage who elect to undergo colonic PT are clean for stool. Greater colon length correlates with success. This suggests that multiple factors, including colon length, are important when considering PT in a child with CE.
III.
Expertise Area 1.2: Bladder exstrophy/epispadias
2024, Rare and Complex Urology
The bladder exstrophy-epispadias complex (BEEC) is a congenital abnormality that involves the abdominal wall, bony pelvis, urinary tract, external genitalia, and in the worse cases, also the gastrointestinal tract. The severity-spectrum of the BEEC comprises the mildest form, isolated epispadias, the classic bladder exstrophy, and the most severe form, cloacal exstrophy, which is often referred to as the OEIS complex (omphalocele, exstrophy, imperforate anus, and spinal defects). This chapter attempts to give comprehensive outlines of the current management, focusing on classic bladder exstrophy. It is clear that there is a lack of universal guidelines. The results of different approaches are still taken with precautions as from the beginning the malformations are far from homogenous with consistent findings. The long-term results on the function and quality of life of these children further on in their adult lives underline the importance of lifelong follow-up and the need for more clinical research, including larger cohorts, to enable expert centres to give an objective global view of the results of different approaches and management.
The complexity of managing the exstrophy is secondary to the difficulty of reconstructing a compliant and functional vesico-sphincteric complex. Adding to this challenge is the reconstruction of functional genitalia.
Tremendous progress has been achieved in surgical procedures to reconstruct bladder exstrophy over the last two decades. The main targets are to achieve a voiding urethra with good bladder capacity and functional genitalia. These difficult targets should be achieved together with preserving the upper urinary tract. Many surgical options are suggested to reach these targets. The controversies between staged reconstruction and primary complete repair are still valid and ongoing. Nevertheless, the majority of exstrophy surgeons accept the surgical principle that mobilisation of the pelvic soft tissue is essential in any bladder exstrophy procedure. This chapter describes two strategies used in two European high-volume centres.
The most recently reported results are encouraging regarding the possibility of volitional continence when applying modern reconstruction techniques. Meanwhile, the incidence of progressive or severe hydronephrosis and/or renal scarring has been reported in up to a third of the patients in specialised centres after bladder exstrophy reconstruction. Balancing volitional continence and low-voiding pressure is the most problematic task in exstrophy.
The clinical outcomes relating to continence need to be completed by critically evaluating bladder function, especially in children not under clean intermittent catheterisation (CIC). The major target of this evaluation is the early detection of a high-risk bladder so the upper tract avoids any irreversible deterioration of kidney function. When initiating the treatment of bladder exstrophy, it is important to include the therapeutic option of CIC. This should be discussed with the patients and their families so that it can be safely utilised when necessary.
The other challenge is genital reconstruction, both in boys and girls. In boys, there is still a crucial lack of long-term results on erectile function after reconstructions. The current long-term studies clearly emphasise the major sexual dysfunction in men operated on for exstrophy. Studies on fertility in men and women are now available.
We hope that new surgical methods and increased centralisation of care by multidisciplinary teams will improve the long-term results in these patients.
Bladder Neck Surgery is not Routinely Needed to Achieve Urinary Continence in Patients with Primary Epispadias
2024, Journal of Pediatric Surgery
This study aims at investigating the continence outcome in primary epispadias patients treated at a tertiary center. The authors hypothesized that additional continence procedures following primary epispadias repair is not routinely needed.
Patients treated for primary epispadias at the authors’ institution between 2007 and 2019 and toilet trained, were identified from a prospective maintained database. Males underwent chordee correction, urethroplasty and glanuloplasty. Females underwent genitoplasty with reduction urethroplasty. If continence was not achieved by 4–5 years of age, pelvic floor muscle (PFM) biofeedback therapy was performed. Other continent procedures were discussed with family/patient if still incontinent. Primary outcome: urinary continence. Secondary outcomes: PFM biofeedback therapy, continence surgery, hydronephrosis. Type of epispadias, age at repair and follow-up presented as median was also reported.
Thirty-three patients (29 males) were included. Twelve had penopubic epispadias, 13 glanular/penile, 4 duplicated urethra, 4 females. Median age at repair: 2 years (IQR 1–3), at follow-up: 8 years (IQR 6–10). Daytime continence: 100 % in penile/glanular; 33 % in penopubic and 75 % in duplicated urethra. Nighttime continence: respectively 92 %, 50 % and 100 %. 24 % of males were intermittently incontinent. All patients except one voided urethrally. One patient underwent bladder neck closure, ileocystoplasty and Mitrofanoff. One girl achieved daytime continence, 2 were intermittently incontinent, one continuously incontinent. All were enuretic. 38 % of boys and 100 % of girls had biofeedback therapy. None had hydronephrosis/renal impairment.
Most children with primary epispadias can achieve social urinary continence spontaneously or with the support of PFM biofeedback therapy. Other continence procedures should be reserved for patients who do not attain satisfactory continence.
Treatment study – level IV.
Mucosal Violations and Their Effect on Successful Bladder Neck Closure in Cloacal Exstrophy
2023, Journal of Pediatric Surgery
Cloacal exstrophy (CE) is rare and challenging to reconstruct. In the majority of CE patients voided continence cannot be achieved and so patients often undergo bladder neck closure (BNC). Prior mucosal violations (MVs), a surgical event when the bladder mucosa was opened or closed, significantly predicted failed BNC in classic bladder exstrophy with an increased likelihood of failure after 3 or more MVs. The aim of this study was to assess predictors for failed BNC in CE.
CE patients who underwent BNC were reviewed for risk factors for failure including osteotomy use, successful primary closure, and number of MVs. Chi-squared and Fisher's exact tests were used for comparing baseline characteristics and surgical details.
Thirty-five patients underwent BNC. Eleven patients (31.4%) failed BNC including a vesicoperineal fistula in nine, vesicourethral and vesicocutaneous fistula in one each. The fistula rate in patients with 2 or more MVs was 47.4% (p = 0.0252). Two patients subsequently developed a vesicocutaneous fistula after undergoing repeated cystolithotomies. A rectus abdominis or gracilis muscle flap were used to close the fistula in 11 and 2 patients, respectively.
MVs have a greater impact in CE with an increased risk of failed BNC after 2 MVs. CE patients are most likely to develop a vesicoperineal fistula while a vesicocutaneous fistula is more likely after repeat cystolithotomy. A prophylactic muscle flap should be considered at time of BNC in patients with 2 or more MVs.
Prognosis Study, Level III.
The impact of repeated bladder surgery on successful bladder neck closure in classic bladder exstrophy: The role of mucosal violations
2023, Journal of Pediatric Urology
Restoration of genitourinary anatomy with functional urinary continence is the reconstruction aim is the exstrophy-epispadias complex (EEC). In patients who do not achieve urinary continence or those who are not a candidate for bladder neck reconstruction (BNR), bladder neck closure (BNC) is considered. Interposing layers including human acellular dermis (HAD) and pedicled adipose tissue are routinely placed between the transected bladder neck and distal urethral stump to reinforce the BNC and minimize failure due to fistula development from the bladder.
The aim of this study was to review classic bladder exstrophy (CBE) patients who underwent BNC to identify predictors of BNC failure. Specifically, we hypothesize that increased operations on the bladder urothelium leads to a higher rate of urinary fistula.
CBE patients who underwent BNC were reviewed for predictors of failed BNC which was defined as bladder fistula development. Predictors included prior osteotomy, interposing tissue layer use and number of previous bladder mucosal violations (MV). A MV was defined as a procedure when the bladder mucosa was opened or closed for: exstrophy closure(s), BNR, augmentation cystoplasty or ureteral re-implantation. Predictors were evaluated using multivariate logistic regression.
A total of 192 patients underwent BNC of which 23 failed. Patients were more likely to develop a fistula with a wider pubic diastasis at time of primary exstrophy closure (4.4 vs 4.0 cm, p=0.0016), have failed exstrophy closure (p=0.0084), or have 3 or more MVs before BNC (p=0.0002). Kaplan-Meier analysis of fistula-free survival after BNC, demonstrated an increased fistula rate with additional MVs (p=0.0004, Figure 1). MVs remained significant on multivariate logistic regression analysis with a per-violation odds ratio of 5.1 (p<0.0001). Of the 23 failed BNC’s, 16 were surgically closed including 9 using a pedicled rectus abdominis muscle flap which was secured to the bladder and pelvic floor.
This study conceptualized MVs and their role in bladder viability. Increased MVs confer an increased risk of failed BNC. When considering BNC, CBE patients with 3 or more prior MVs may benefit from a pedicled muscle flap, in addition to HAD and pedicled adipose tissue, to prevent fistula development by providing wellvascularized coverage to further reinforce the BNC.
Narrowing the chromosome 22q11.2 locus duplicated in bladder exstrophy–epispadias complex
2022, Journal of Pediatric Urology
Citation Excerpt :
In a Europe-wide prospective survey, 238 affected individuals with BEEC were reported to be born in a single year [11]. Here, CBE was the most common form, with an estimated birth incidence of 1/46,000 [11]. Given that certain other urinary tract malformations can have defined genetic bases, as outlined above, we, and others, have considered that BEEC could have one or more genetic causes.
Bladder exstrophy–epispadias complex (BEEC) comprises a spectrum of anterior midline congenital malformations, involving the lower urinary tract. BEEC is usually sporadic, but families with more than one affected member have been reported, and a twin concordance study supported a genetic contribution to pathogenesis. Moreover, diverse chromosomal aberrations have been reported in a small subset of individuals with BEEC. The commonest are 22q11.2 microduplications, identified in approximately 3% of BEEC index cases.
We aimed to refine the chromosome 22q11.2 locus, and to determine whether the encompassed genes are expressed in normal developing and mature human urinary bladders.
Using DNA from an individual with CBE, the 22q11.2 duplicated locus was refined by identification of a maternally inherited 314 kb duplication (chr22:21,147,293–21,461,017), as depicted in this image.
Moreover, the eight protein coding genes within the locus were found to be expressed during normal developing and mature bladders. To determine whether duplications in any of these individual genes were associated with CBE, we undertook copy number analyses in 115 individuals with CBE without duplications of the whole locus. No duplications of individual genes were found.
The current study has refined the 22q11.2 locus associated with BEEC and has shown that the eight protein coding genes are expressed in human bladders both during antenatal development and postnatally. Nevertheless, the precise biological explanation as to why duplication of the phenocritical region of 22q11 confers increased susceptibility to BEEC remains to be determined. The fact that individuals with CBE without duplications of the whole locus also lacked duplication of any of the individual genes suggests that in individuals with BEEC and duplication of the 22q11.2 locus altered dosage of more than one gene may be important in BEEC etiology.
The study has refined the 22q11.2 locus associated with BEEC and has shown that the eight protein coding genes within this locus are expressed in human bladders.

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Prospective study on the incidence of bladder/cloacal exstrophy and epispadias in Europe

Summary

Objective

Study design

Results

Discussion

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Conclusion

Conflict of interest

Funding

Acknowledgments

Eur J Med Genet

J Pediatr Urol

J Urol

J Urol

Exstrophy of the bladder, epispadias, and other bladder anomalies

Epidemiology of bladder exstrophy and epispadias: a communication from the international clearinghouse for birth defects monitoring systems

Teratology